Clinical trial NCT04200456
Conditions: Primary Immune Thrombocytopenia
Keywords: ITP UCB7665 Rozanolixizumab Primary immune thrombocytopenia
Sponsor: UCB Biopharma SRL
Start date: 2020-01-31; Completion date: 2022-04-27
Enrollment: 33 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to demonstrate the clinical efficacy of rozanolixizumab in maintenance treatment and assess safety and tolerability of rozanolixizumab in adult study participants with primary immune thrombocytopenia (ITP).

Detailed description:

Arms: arm 1: Study participants randomized to this arm will receive fixed-unit doses of rozanolixizumab across body weight tiers at pre-specified time points during the Treatment Period. Doses will be adjusted based on platelet count values or medical needs. arm 2: Study participants randomized to this arm receive placebo at pre-specified time points during the Treatment Period.
Interventions: intervention 1: Rozanolixizumab intervention 2: Placebo
Intervention descriptions: intervention 1: Study participants receive rozanolixizumab by subcutaneous infusion at pre-specified time points. intervention 2: Study participants receive placebo by subcutaneous infusion at pre-specified time points.

Protocol documents:
Prot_000.pdf: 
UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 1 of 220
A PHASE 3 MULTICENTER, DOUBLE-BLIND, RANDOMIZED, 
PLACEBO-CONTROLLED STUDY TO EVALUATE THE
EFFICACY, SAFETY, AND TOLERABILITY OF 
ROZANOLIXIZUMAB IN ADULT STUDY PARTICIPANTS WITH 
PERSISTENT OR CHRONIC PRIMARY IMMUNE 
THROMBOCYTOPENIA (ITP)
PROTOCOL TP0003 AMENDMENT 3
PHASE 3
Short title:
A Phase 3 study evaluating the efficacy, safety, and tolerability of rozanolixizumab in adult 
study participants with ITP
Sponsor:
UCB Biopharma SRL
Allée de la Recherche 60
1070 Brussels
BELGIUM
Regulatory agency identifying number:
EudraCT Number:
2019-000884-26
IND Number
143499
NCT Number
NCT04200456
Confidential Material
Confidential
This document is the property of UCB and may not – in full or in part – be passed on, 
reproduced, published, or otherwise used without the express permission of UCB.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 2 of 220
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
Document History
Document
Date
Type of amendment
Protocol Amendment 3
03 Dec 2021
Substantial 
Protocol Amendment 2
29 Sep 2020
Substantial
Protocol Amendment 1.3
(France)
27 Apr 2020
Substantial
Protocol Amendment 1.2 
(Japan)
16 Mar 2020
Substantial
Protocol Amendment 1.1 
(US and Canada)
21 Feb 2020
Substantial
Protocol Amendment 1
21 Nov 2019
Substantial
Original Protocol
27 Sep 2019
Not applicable
Amendment 3 (03 Dec 2021)
Overall Rationale for the Amendment
The primary reason for this protocol amendment is the recommendation of the external 
Independent Data Monitoring Committee (IDMC) to modify the dosing regimen of the study.
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union.
Section # and Name
Description of Change
Brief Rationale
Global 
IMP dosing every 2 weeks was updated to 
weekly dosing.
Updated based on the 
feedback from the IDMC 
recommending the option 
to increase the frequency in 
dosing, to reduce the 
potential risks associated 
with low platelet counts.
Serious adverse event 
reporting
For serious adverse event reporting (24h), 
the fax number for Japan has been 
removed.
A separate fax number for 
Japan is no longer 
applicable as reporting in 
Japan should be done under 
the ROW or US fax 
number. 
1.1 Synopsis, Objectives 
and endpoints
3 Objectives and endpoints
The secondary efficacy endpoint for the 
ITP-PAQ was updated to delete “including 
all intermediate timepoints”.
Intermediate timepoints 
were removed based on 
FDA feedback. 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 3 of 220
Section # and Name
Description of Change
Brief Rationale
1.1 Synopsis, Objectives 
and endpoints
3 Objectives and endpoints
The other safety endpoint “Change from 
Baseline in concentrations of total protein, 
and albumin, α globulin, and β globulin 
was updated to “Change from Baseline in 
concentrations of total protein and 
albumin”.
The other safety endpoint “Change from 
Baseline in cytokines during the study (for 
study participants experiencing infusion 
reactions or hypersensitivity reactions)” 
was deleted.
The endpoint was removed 
to decrease study 
complexity, as scientific 
value is limited.
The endpoint was removed 
as the analysis of cytokines 
is not required in the ITP 
protocols as samples have 
been collected in other 
rozanolixizumab studies 
and no additional 
information is expected 
from the ITP population.
1.1 Synopsis, Objectives 
and endpoints
3 Objectives and endpoints
The following exploratory PD endpoints 
were updated as follows: 
“Minimum value in total serum IgG and 
maximum decrease from Baseline in total 
serum IgG concentration” was deleted.
“Change from Baseline in serum IgG and 
in serum IgG subclass concentration” was 
updated to “Total serum IgG (absolute 
value) and change from Baseline (absolute 
value and percentage) in serum IgG and in 
serum IgG subclass concentration at each 
scheduled assessment”
“Change from Baseline in serum 
immunoglobulin concentrations (IgA, IgE, 
IgM)” was updated to “Absolute value and 
change from Baseline (absolute value and 
percentage) in serum immunoglobulin 
concentrations (IgA, IgE, IgM) at each 
scheduled assessment”
“Change from Baseline in ITP-specific 
autoantibodies in serum” was deleted
Deleted as this variable 
will be followed at every 
scheduled visit rather than 
only reporting the lowest 
value across the duration of 
the study
Endpoint was amended to 
provide further details of 
the endpoint and to add 
clarity.
Endpoint was amended to 
provide further details of 
the endpoint and to add 
clarity.
The endpoint was deleted 
as the results of the 
analysis will not be part of 
the CSR of this study and 
will be described in a 
separate report.
1.1 Synopsis, Objectives 
and endpoints
The objective “To evaluate the effects of 
rozanolixizumab on exploratory 
Objective and endpoint 
were removed as the 
exploratory biomarker 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 4 of 220
Section # and Name
Description of Change
Brief Rationale
3 Objectives and endpoints
biomarkers” and its associated endpoints 
were removed. 
samples are taken for 
future analysis, with no 
predefined analysis 
objective and endpoints.
1.1 Synopsis, Objectives 
and endpoints
3 Objectives and endpoints
The following exploratory objective and 
endpoint were added:
Objective: To assess the effect of 
rozanolixizumab on response to 
vaccination in study participants who 
received COVID-19 vaccine
Endpoint: Change in biomarkers of 
COVID-19 vaccine response over time
New objective and 
endpoint are needed for the 
collection of information 
on post-vaccination 
biomarkers for participants 
who have received the 
COVID-19 vaccination.
1.1 Synopsis, Overall 
design
4.1 Overall design
The vaccination requirements for 
splenectomized participants were updated. 
The requirement for vaccination titers
assessment for eligibility purposes was 
removed. 
Updated for consistency 
with the changes done in 
Section 8.2.6. 
1.1 Synopsis, Overall 
design
4.1 Overall design
The sentence regarding home visits was 
updated to state that home visits including 
home dosing and assessments as per 
Section 1.3 can be conducted once all pre-
requisites for a home dosing visit are 
fulfilled. 
Updated for consistency. 
1.1 Synopsis, Overall 
design
4.1 Overall design
The one-time fixed unit starting dose of 
rozanolixizumab equivalent to 
 or 
placebo was removed. 
Deleted because of the new 
dose regimen of 
 
 once a week. A 
 QW 
dose regimen is anticipated 
to achieve similar level of 
receptor occupancy (RO)% 
to a 
, with a range on RO% 
from peak to trough of 99 
to 50% during the 7 days 
dosing interval.
1.1 Synopsis, Overall 
design
4.1 Overall design
Week 13 was updated to Week 12.
Updated to correct an error.
1.1 Synopsis, Overall 
design
4.1 Overall design
Platelet count of “≥50×109/L to 
200×109/L” was updated to “≥50×109/L to 
≤150×109/L”.
For consistency to other 
changes in the protocol. 
1.1 Synopsis, Overall 
design, Table 1-1 Dose 
The following text was added or updated:
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 5 of 220
Section # and Name
Description of Change
Brief Rationale
adjustments of IMP 
following initial dose, 
Figure 1-1 TP0003 dose 
adjustments of IMP
4.1 Overall design
Platelet count of <10×109/L, rescue therapy 
is highly recommended. 
Platelet count of ≥10×109/L to <30×109/L
(on at least two consecutive visits), rescue 
therapy is recommended. 
Platelet count of <50×109/L was updated to 
≥30×109/L to <50×109/L, Dose adjustment 
instructions were updated to "dose level 
can be increased unless the study 
participant is on a maintenance dose of 
". 
Platelet count of ≥50×109/L to ≤200×109/L 
was updated to ≥50×109/L to ≤150×109/L. 
Platelet count of >200×109/L to 
<400×109/L was updated to ≥150×109/L to 
<400×109/L
For platelet counts of ≥400×109/L, 
instructions were updated to “Stop IMP 
treatment. Once the platelet count is 
≤150×109/L reinitiate treatment decreased 
by one dose level”.
The text regarding interindividual variable 
platelet response was moved as table 
footnote b.
Updated to provide further 
guidance on when rescue 
medication is highly 
recommended or 
recommended
Updated to permit 
reduction in dose earlier in 
the event of a platelet
increase given the change 
to a weekly dosing 
regimen
Updated in order to clarify 
that all study participants 
with platelet counts 
≤150×109/L should 
reinitiate treatment with a 
dose decreased with one 
level.
Updated to provide clarity 
that the text belongs to 
Table 1-1.
1.1 Synopsis, Overall 
design
4.1 Overall design
The visit window upon rollover from 
TP0003 or TP0006 into TP0004 has been 
updated from 1 week to 3 days. 
The requirement for a SFU visit in between 
the rollover, and the requirement for 
platelet count measurement in case of a late 
rollover, have both been removed. 
Day 211 was updated to Day 218.
Updated for consistency 
with the weekly dosing 
regimen and for 
consistency throughout the 
protocol.
1.1 Synopsis, Overall 
design
4.1 Overall design
The following paragraph was added:
Based on feedback from the IDMC, weekly 
dosing was implemented in protocol 
amendment 3. Study participants being 
treated with the bi-weekly dosing regimen 
To clarify the dosing for 
existing study participants 
receiving bi-weekly dosing.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 6 of 220
Section # and Name
Description of Change
Brief Rationale
will switch to the weekly dosing regimen 
once protocol amendment 3 is approved at 
the respective study site.
1.1 Synopsis, Number of 
study participants
4.1 Overall design
The two-stage statistical design and interim 
analysis were deleted. 
The target number of study participants 
was updated to 90, at least 60 of which will 
be randomized to weekly IMP 
administration. 
Updated for consistency 
with the change in dosing 
regimen and to reflect 
current statistical analysis 
plans.
1.1 Synopsis, Treatment 
groups and duration
4.1 Overall design
The total maximum study duration per 
study participants was updated to 
35 weeks. 
Updated as the final dose 
will be administered at 
Week 24 instead of Week 
23 and therefore the final 
visit (8 weeks after the 
final dose) was moved to 
Week 32.
1.1 Synopsis, Treatment 
groups and duration
4.1 Overall design
The Prolonged Screening Period for 
splenectomized participants was updated 
from 14 weeks to 20 weeks.
Updated for improving 
study participants' 
experience in the study by 
decreasing the time 
pressure on the vaccination 
schedule.
1.1 Synopsis, Treatment 
groups and duration, Table 
1-2 TP0003 dose levels 
and weight tiers of IMP
The table title was updated from “TP0003 
dose levels and weight tiers of 
rozanolixizumab” to “TP0003 dose levels 
and weight tiers of IMP”.
The one-time fixed unit starting dose of 
rozanolixizumab equivalent to 
 or 
placebo was removed. 
Reference to “maintenance dose” was 
removed in the table headers. 
Platelet count of >200×109/L was updated 
to >150×109/L in the table footnote.
Table title was corrected.
Deleted as the 
 
starting dose is 
no longer required with the 
new dosing regimen of 
 once a week.
Updated for consistency 
with the changes in Table 
1-1.
1.2 Schema, Figure 1-2 
TP0003 study schematic
IMP dosing every 2 weeks was updated to 
weekly dosing. 
The one-time fixed unit starting dose of 
rozanolixizumab equivalent to 
 or 
placebo was removed. 
Updated upon request from 
the IDMC 
Updated as the 
 
 starting dose is 
no longer needed with the 
new dose regimen of 
 once a 
week.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 7 of 220
Section # and Name
Description of Change
Brief Rationale
The dose adjustment period was corrected 
to Week 1 to 12. 
The total maximum study duration per 
study participants was updated to 35 
weeks. 
The Safety Follow-up Period was updated 
to 7 weeks after Week 25 leading to the 
last visit moving to Week 32.
Figure footnote relating to the Prolonged 
Screening Period for splenectomized 
participants was updated from 14 weeks to 
20 weeks. 
Updated for clarity
Updated for consistency 
with the weekly dosing 
regimen
Updated for consistency 
with the weekly dosing and 
last dosing being Week 24. 
Updated for consistency 
with the changes in 
Sections 1.1 and 4.1.
Table 1-3 Schedule of 
activities (Prolonged 
Screening only for 
splenectomized study 
participants)
Prolonged Screening was extended to 20 
weeks.
Vaccination titers prior to vaccination and 
post vaccination titers during the Prolonged 
Screening Period and its associated 
footnotes were removed. 
An additional footnote was added to state 
that Inclusion criterion #8 is not applicable 
for the Prolonged Screening Period. Study 
participants may take ITP concomitant 
medication as per Table 6-2.
Updated for consistency 
with the changes in Section 
1.1 and Section 4.1.
Updated for consistency 
with the changes done in 
Section 8.2.6.
Updated to clarify that the 
splenectomized study 
participants needing 
vaccination do not need to 
have low platelet counts 
throughout the Prolonged 
Screening Period.
Table 1-4 Schedule of 
activities
IMP dosing every 2 weeks was updated to 
weekly dosing. Call to IRT for treatment 
kit number was updated accordingly.
Day 5 (Week 1, Visit 4) was deleted. 
Subsequent visit numbering was updated 
accordingly. 
Concomitant medical procedures, vital 
signs and recording of AEs were added to 
each visit following Baseline. 
The EOS Visit was amended from W31, 
Day 211 to W32, Day 218.
Updated to harmonize the 
assessments and visits with 
the change in dosing 
regimen and to provide 
consistency with other 
changes made to the 
protocol that are outlined in 
this section of the 
protocol.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 8 of 220
Section # and Name
Description of Change
Brief Rationale
Column related to home visits have been 
grayed out.
Notes were added to clarify white columns 
are site visits and gray column refers to 
optional home visits. Additional text was 
added to state “Home IMP administration 
and assessments are optional and can be 
conducted (if approved by regulatory 
agencies) at the sites as deemed necessary 
by site personnel and/or the study 
participant.”
Footnote “a” regarding home visits, was 
deleted.
A new footnote “a” was added: The 
allowed time window for assessments is 
±5 mins for assessments <30 mins and 
±15 mins for assessments >30 mins.
Footnote d was updated to: The visit 
windows are relative to the Dosing Visit 1 
date. At Day 3 a visit window of +2 days is 
allowed. For all remaining visits a visit 
window of +/-2 days is allowed. However 
there should be a minimum interval of 
5 days and a maximum interval of 9 days 
between two doses of IMP.
Footnote g: was updated to state that the 
last available platelet count can be
considered rather than the last two 
available platelet counts. 
A new footnote “h” was added to state that 
platelet counts can be taken at home visits; 
home visits are allowed if the previous 4 
platelet counts were stable between 50 to 
150×109/L and there was no dose change. 
If criteria are met, the visit may be 
conducted at home, administering the same 
dose of IMP as for the previous visit.
Footnote h, now i: was updated with vital 
signs assessment timepoints. 
Footnote i, now j: was updated to remove 
triplicate and three ECGs.
Footnote j now k: was updated to delete the 
vaccination titer sample at the Screening 
visit and W13 and a sample at Baseline 
was added. 
Footnote k was moved from Screening to 
the assessment name. 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 9 of 220
Section # and Name
Description of Change
Brief Rationale
Footnote l relating to vaccination titers 
against tetanus was deleted. 
Footnotes m, n and o relating to the IGRA 
test and TB chest x-ray were deleted. 
COVID-19 biomarkers sampling and 
associated footnotes (footnote “m” and 
“n”) were added. 
Footnote r  relating to the starting dose 
equivalent to 
 was deleted. 
Footnote s relating to the IMP 
was deleted.
Footnote q now p: was updated with more 
details on post-dose observation.
Footnote u now r: was updated to reflect 
the PK and ADA sampling times. 
Footnote v now s and footnote y now u: 
were updated to include sample collection 
at Baseline (Day 1) and W25 for all study 
participants.
Footnote w regarding serum and plasma 
complements and cytokines at W23 4 
hours postdose was deleted. 
A new footnote “v” was added to state “If 
total IgG levels are <1g/L, ad hoc 
assessments (eg, additional IgG samples) 
may be performed to monitor recovery of 
IgG levels. See Section 10.25”
Footnote ‘y’ (formerly footnote ‘aa’) was 
updated to state that the assessment can 
also be done remotely eg, via phone 
interview. 
The IGRA TB test and chest x-ray were 
deleted. 
Samples for cytokines were removed. 
2.2 Background 
IMP dosing every 2 weeks was updated to 
weekly dosing. 
The one-time fixed unit starting dose of 
rozanolixizumab equivalent to 
 or 
placebo was removed.
CIDP04, MG0004 and MG0007 were 
added as ongoing studies. CIDP01 was 
added to the list of completed studies.
A summary of the safety data from 
Updated for consistency 
with the change in dosing 
regimen, and with relevant 
completed or ongoing 
study information.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 10 of 220
Section # and Name
Description of Change
Brief Rationale
CIDP01 was added.
Brief details about CIDP04 were added. 
2.3 Benefit/risk assessment The Benefit/risk assessment was updated to 
include recommendations regarding 
COVID-19 vaccinations and to remove 
“important potential risks” such as effects 
on the kidney, and reductions in albumin 
and plasma proteins. 
Updated to be consistent 
across the Phase 3 
rozanolixizumab clinical 
program.
4.1 Overall design 
The text regarding post-dose observation 
time following the end of infusion was 
updated. 
Day 211 was updated to Day 218.
The text on rozanolixizumab infusion was 
updated.
Updated to be consistent 
across the Phase 3 
rozanolixizumab clinical 
program.
4.2 Scientific rationale for 
study design 
IMP dosing every 2 weeks until Week 23 
was updated to weekly dosing until
Week 24.
Details of the number of study participants 
from CIDP01 and CIDP04 treated 
 
with 
 rozanolixizumab were 
added.
Updated for consistency 
with the change in dosing 
regimen and to provide 
additional data in support 
of the 
 
 
dosing regimen.
4.3 Justification for dose 
A more frequent dosing regimen of 
 once per week is 
introduced in TP0003,TP0006 and the  
OLE TP0004 study. 
The 
 starting dose is 
removed from the protocol.
The change follows the 
advice of the external 
IDMC on a more frequent 
dosing regimen, following 
the review of the platelet 
data from TP0004, where 
platelets are not sustained 
at the desired level within 
the 
.
4.4 End of study definition 
6.6 Treatment after the end 
of the study
The visit window of 1 week for rollover 
into TP0004 was updated to 3 days. 
Visit numbers were updated according to 
updated schedule of activities. 
The SFU Visit to be conducted in between 
rollover was deleted. 
The text “In case of late rollover, platelet 
counts will need to be remeasured” was 
deleted. 
Updated for consistency 
with the 
 dosing 
regimen and for 
consistency throughout the 
protocol.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 11 of 220
Section # and Name
Description of Change
Brief Rationale
5.1 Inclusion criteria 
Inclusion criterion 4a, now 4b, was 
updated to clarify ITP treatments and to 
add splenectomy. 
Updated for clarity.
5.1 Inclusion criteria 
Inclusion criterion #12, now 12a, was 
updated to correct “or” to “and”
“as confirmed by a negative pregnancy test 
and not planning to get pregnant”.
The sentence was 
corrected. 
5.2 Exclusion criteria
Exclusion criterion 2, now 2a, updated to 
clarify ‘current’ anticoagulant treatment. 
Cross-reference to Table 5-1 was added. 
Exclusion criterion 7a, now 7b was 
updated to clarify a clear association with 
other medical conditions. 
Exclusion criterion 15 regarding Karnofsky 
Performance Status was removed. 
Exclusion criterion 20a, now 20b was 
updated to remove the requirement for S. 
pneumoniae, N. meningitidis and H. 
influenzae vaccine titers during the 
Prolonged Screening Period.
Exclusion criteria 22, 23a, 27, and 29 were 
removed. 
In Table 5-1, the cross reference to 
Exclusion Criterion 23a was removed and 
the corresponding exclusionary 
requirements were added to Table 5-1.. 
Exclusion Criterion 33a, now 33b, was 
amended to remove the following bullet 
point: ALT, AST, or ALP results up to 
25% above the exclusion limit may be 
repeated once for confirmation, including 
rescreening. 
Exclusion criterion 42 was removed. 
Updated to provide 
additional clarity to certain 
exclusion criteria, remove 
redundancies and ensure 
consistency throughout the 
protocol.
The Karnofsky score is 
generally used for 
predicting the length of 
survival in terminally ill 
patients. This score was 
considered as not suited for 
the target patient 
population for the study
and removed.
Updated to provide 
additional clarity to certain 
exclusion criteria, remove 
redundancies and ensure 
consistency throughout the 
protocol.
5.4 Screen failures 
References to IGRA TB tests and tests that 
result in ALT, AST, or ALP up to 25% the 
exclusion limit have been removed. 
Updated for consistency of 
the respective changes 
throughout the protocol.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 12 of 220
Section # and Name
Description of Change
Brief Rationale
5.4 Screen failures
The wording about vaccination for 
splenectomized participants was updated. 
Updated for consistency 
with the changes done in 
Section 8.2.6.
6 Study Treatments, Table 
6-1 Treatments 
administered 
IMP dosing every 2 weeks was updated to 
weekly dosing. 
The one-time fixed unit starting dose of 
rozanolixizumab 
was removed.
Updated for consistency 
with the change in dosing 
regimen.
6 Study Treatments, Table 
6-1 Treatments 
administered
References to vial fill volumes was 
removed. 
Updated to reflect the 
foreseeable change in vial 
fill volumes.
6 Study Treatments, Table 
6-1 Treatments 
administered
Dosing instructions were updated. 
To align with the latest 
dosing instructions. 
6 Study Treatments, Table 
6-1 Treatments 
administered
Reference to Canada was removed.
Updated as Canada is not 
participating in TP0003. 
6.2.1.1 Maintenance of 
study treatment blind
Bullet point #2 was updated to delete “on 
request”.
To align with the current 
procedure.
6.2.1.1 Maintenance of 
study treatment blind
The text was updated to state the procedure 
in case the serum IgG level decreases to 
<1g/L. A cross reference to Appendix 25 
was added.
Updated to ensure 
consistency with the 
changes in Section 10.25.
6.3 Treatment compliance
The text was updated to add “study 
participant’s home”. 
Updated as optional home 
dosing visits have been 
included in the schedule. 
6.4.1 Permitted 
concomitant treatments 
(medications and 
therapies)
The text was updated to clarify that the 
following concomitant medications are 
permitted during the study and if possible, 
kept stable for the duration of the study.
Updated to clarify that if 
possible, the permitted 
concomitant medications 
should be kept at a stable 
dose for the duration of the 
study.
6.4.1 Permitted 
concomitant treatments 
(medications and 
therapies)
Table 6-2 Permitted 
concomitant treatments 
(medications and 
therapies)
Permitted oral corticosteroids dose was 
increased to ≤20mg/day.
A dose of "≤4mg/kg/day for modified" was 
added for cyclosporin.
Allowed dose of oral 
corticosteroids was 
increased to a maximum of 
20 mg/day for more 
flexibility in managing the 
concomitant ITP treatment. 
Updated to clarify 
permitted concomitant 
medications.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 13 of 220
Section # and Name
Description of Change
Brief Rationale
6.4.3 Rescue therapy 
The conditions to commence IMP 
treatment following rescue therapy with 
high dose corticosteroids were updated.
Permitted oral corticosteroids dose was 
updated to 20mg/day.  
Updated for consistency 
with the new dosing 
regimen and other allowed 
rescue medication (platelet 
count is considered the 
more clinically relevant 
trigger for IMP initiation 
compared with a strict time 
interval of 4 weeks). 
6.4.3 Rescue therapy
Text was updated to state that details of the 
rescue therapy administered must be 
recorded in the eCRF. 
Updated for clarity. 
6.5 Dose modification 
Text pertaining to dose modification was 
modified to clarify that dose modifications 
of the IMP were permitted in order to 
maintain the platelet counts between 
≥50×109/L and ≤150×109/L. References to 
up and down titration of the IMP was 
deleted. Additional text was added to state 
“Dose modifications or temporary 
discontinuation of IMP treatment are 
permitted if serum IgG value is <1g/L 
(Section 10.26)”.
Updated to reflect that 
platelet counts should be 
maintained between 
≥50×109/L and 
≤150×109/L. 
Added to provide clarity 
that dose modifications 
based on IgG values are 
permitted.
6.5 Dose modification
An additional bullet point regarding 
moderate to severe toxicities was added. 
Updated to remain 
consistent with the 
rozanolixizumab program.
7.1.2 QTc stopping criteria
“Average of triplicate” ECG was removed. 
Updated to reflect the 
changes in Section 8.1.3.
7.1.3 Discontinuation of 
IMP due to other adverse 
events or medical 
condition
The text was updated to ” Study participant 
has a significant infective episode 
including but not limited to: bacteremia or 
sepsis, infectious meningitis, osteomyelitis, 
septic arthritis, complicated pneumonia or 
visceral abscess which may or may not 
result in hospitalization. This list is not 
intended to be all inclusive, and the 
investigator is expected to apply his/her 
judgment on continuing IMP based on the 
clinical situation at hand”
Updated to reflect the 
current general program
guidance.
7.1.3 Discontinuation of 
IMP due to other adverse 
events or medical 
condition
The text was updated as follows: Study 
participant has a serious AE of headache or 
GI disturbance that is considered related to 
the IMP in the opinion of the investigator; 
or recurrent severe AE of headache (see 
Appendix 22, Section 10.22) or GI 
disturbance that is considered related to the 
Updated to remain 
consistent with Phase 3 ITP 
clinical program.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 14 of 220
Section # and Name
Description of Change
Brief Rationale
IMP in the opinion of the investigator (See 
Appendix 23, Section 10.23).
7.1.3 Discontinuation of 
IMP due to other adverse 
events or medical 
condition
Reference to TB test was removed. 
Updated for consistency 
with the changes in Section 
8.2.5.
7.1.4 Temporary IMP 
discontinuation
Instructions for temporary IMP 
discontinuation were updated to remove 
individual requirements for splenectomized 
and non-splenectomized participants. 
Updated to ensure 
consistency with the 
changes in Section 10.25.
7.1.4 Temporary IMP 
discontinuation
Instructions in relation to restarting IMP 
following COVID-19 infection/exposure 
were updated.
Updated for providing 
additional clarity on the 
temporary IMP 
discontinuation due to 
COVID-19 infection/ 
exposure.
7.1.4 Temporary IMP 
discontinuation
Text was added/updated as follows: 
Study participant MAY temporarily 
discontinue IMP if any of the following 
events occur:
1.
A severe AE of headache that is 
considered related to the IMP in the 
opinion of the investigator 
(Section 10.22)
2.
A splenectomised study participant 
develops a (persistent or re-occurring) 
nonserious infection, as per 
investigator’s decision (Section 10.25)
3.
Total serum IgG value is <1g/L as per 
investigator’s decision. As IMP 
treatment is administered weekly, the 
decision to temporarily hold the 
treatment should be determined based 
on the most recently available total IgG 
value. As the IgG, IgG subtypes, 
albumin and total protein levels will be 
blinded to both the study site personnel 
and the clinical team at the sponsor and 
CRO, unblinded Medical Monitors will 
be monitoring the IgG levels and will 
alert the investigator in case of 
decreases <1g/L. Additionally, 
Updated to ensure 
consistency with the 
changes in Section 10.22 
and Section 10.25.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 15 of 220
Section # and Name
Description of Change
Brief Rationale
guidance for investigators on 
management of infections can be found 
in Appendix 25, Section 10.25.
7.2 Participant 
discontinuation/withdrawal 
from the study
#3 was added as follows: 3. Study 
participant meets the mandatory IMP 
discontinuation criteria as per Section 
7.1.1, Section 7.1.2 or Section 7.1.3 occur.
Added for consistency 
throughout the protocol. 
8 Study assessments and 
procedures 
Additional text was added regarding home-
nursing visits. 
Text added to provide 
additional details on the 
optional home-nursing 
visits and the conditions 
that need to be met prior to 
the conduct of home-
nursing visits.
8.1.1 Platelet counts
The first endpoint was updated to clarify 
that the last 12 weeks refer to Weeks 13 to 
25.
Updated for consistency 
with the Objectives section 
and to provide further 
clarity on the endpoint 
assessment timepoint.
8.2.2 Vital signs
Vital signs measurement time points for all 
visits were updated and clarified. 
Updated for consistency 
with the change in dosing 
regimen and to provide 
consistency across the 
studies in the 
rozanolixizumab 
development program.
8.2.3 Electrocardiograms
Text was updated to remove references to 
triplicate ECGs :“Triplicate 12 lead ECG” 
ECG was replaced with “A 12-lead ECG”.
No identification of cardio-
toxicity from non-clinical 
data, supported by lack of 
signal of cardiac events in 
the rozanolixizumab-
program. Updated in order 
to decrease the burden to 
the sites and study 
participants. 
8.2.5 Assessment and 
management of TB and TB 
risk factors
The text was updated to clarify that 
assessment and management of TB and TB 
risk factors should follow local or national 
guidelines. 
Patients with known 
tuberculosis (TB) infection, 
at high risk of acquiring 
TB infection, or latent 
tuberculosis infection 
(LTBI), or current/history 
of nontuberculous 
mycobacterial infection 
(NTMBI) are already 
excluded from 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 16 of 220
Section # and Name
Description of Change
Brief Rationale
TP0003/TP0006, therefore 
the sites are expected to 
follow national / local 
guidelines for the 
management of TB, in case 
needed.
In addition, the mechanism 
of action of 
rozanolixizumab is 
expected to have little or no 
impact on the immune 
response against 
intracellular organisms 
which is involved in 
controlling the infection 
with Mycobacterium 
tuberculosis.
8.2.5.1 Tuberculosis 
assessment 
Sections on physical examination for TB, 
TB assessment by IGRA, and TB 
assessment by chest x-ray were removed. 
Updated to ensure 
consistency with Section 
8.2.5.
8.2.5.2 Tuberculosis 
management
Text on test conversion for IGRA was 
removed. 
Updated to ensure 
consistency with Section 
8.2.5.
8.1.5.2 Tuberculosis 
management
The definition for LTBI was updated. 
The definitions for active TB and NTMBI 
were added. 
LTBI definition updated as 
per WHO and CDC 
guidelines. Active TB and 
NTMBI definitions as per 
WHO and CDC guidelines 
were added for 
consistency. 
8.2.5.2 Tuberculosis 
management
Text pertaining to AE reporting for Latent 
TB was removed. 
Updated for consistency in 
reporting any TB related 
AEs as per Section 8.2.5.1.
8.2.6 Splenectomized 
study participants 
The vaccination requirements for 
splenectomized participants were updated. 
The requirement for vaccination titers 
collection during Screening was moved to 
Baseline. Vaccination titers at W13 were 
removed. 
Due to the lack of 
evidence-based best 
practice in the area, 
updated to align with the 
general clinical practice 
standards. 
8.3 Adverse events 
A note was added that in order to protect 
the blind, the events of 
hypogammaglobulinemia should not be 
captured as an AE in the eCRF.
The blinded study teams at 
the Sponsor, CRO and site 
must remain blinded in 
case an event of 
hypogammaglobulinemia 
occurs. Only the unblinded 
Medical Monitors and the 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 17 of 220
Section # and Name
Description of Change
Brief Rationale
investigator will have 
access to this information. 
The respective AEs will be 
reconciled based on the 
IgG values at the end of the 
study, after data base lock 
will take place and the data 
will be unblinded. 
8.3.8 Adverse events of 
special monitoring
Text was added to state that the headache 
questionnaire should also be completed in 
case of moderate headache although 
moderate headache is not considered an 
AESM.
Updated to ensure
consistency with the 
changes in Section 10.22.
8.3.10 COVID-19 
vaccination
A new subsection has been included to 
ensure AEs considered related to COVID-
19 vaccination are captured. 
Implemented to ensure 
study participant safety in 
response to the COVID-19 
pandemic.
8.7 Pharmacodynamics 
A sentence was added to state that results 
of the ITP-specific autoantibodies analyses 
will not be outlined in the Clinical Study 
Report for this study.
Analysis of the ITP-
specific autoantibodies is a 
lengthy method and 
therefore the results will be 
provided in a separate 
report.
8.8.2 Immunology 
Serum cytokines were deleted.
Week 23 was updated to Week 25. 
Removed as the scientific 
value of the serum 
cytokines is limited.
Updated to reflect the 
change in the study design 
due to weekly dosing.
8.9 Exploratory 
biomarkers
α- and β-globulins were removed. 
Removed as the scientific 
value of these exploratory 
biomarkers is limited.
9.3.1 Analysis of the 
primary efficacy/primary 
endpoint 
The two-stage statistical design was 
removed. 
Additional wording to clarify that platelet 
count from Week 14 to Week 25 will be 
used to assess durable clinically 
meaningful platelet count was included.
To reflect inclusion of 
weekly sc infusion 
treatment as the primary 
efficacy assessment and the 
requirement to randomize a 
fixed number of 
participants on weekly 
dosing.
Table 9-1 Estimands for 
the primary endpoint 
The RS population was updated to those 
who were randomized to weekly dosing 
compared to placebo. 
Updated to reflect that the 
primary objective is to 
assess the rozanolixizumab 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 18 of 220
Section # and Name
Description of Change
Brief Rationale
Geographical region was removed as a 
stratification factor from the CMH model. 
treatment effect for weekly 
sc infusions.
Geographical region 
removed from the model to 
add convergence of the 
statistical model.  Region 
will be explored through 
subgroup analyses detailed 
in the SAP.
Table 9-2 Estimands for 
secondary endpoints
The RS population was updated to those 
who were randomized to weekly dosing 
compared to placebo. 
Geographical region was removed as a 
stratification factor from the statistical 
models.
Statistical tests were updated.
Geographical region 
removed from the analysis 
models to mirror the 
analysis of the primary 
endpoint.
Statistical tests updated to 
reflect proposed analyses in 
the SAP.
9.3.3.1 Analysis of 
pharmacokinetic endpoint 
The text was updated as follows: “A 
statistical summary of rozanolixizumab 
plasma concentrations will be reported by 
scheduled time point overall and by body 
weight tier, stratified by dose regimen. 
Further details on summaries for dose 
modifications will be provided in the 
corresponding SAP.”
To reflect the change to 
weekly sc infusion 
treatment by summarising 
the data by bi-weekly and 
weekly treatment.
9.3.3.3 Analysis of 
pharmacodynamic 
endpoints
The total IgG endpoint wording was 
updated. 
Updated to reflect that IgG 
will measured and analyzed 
at every scheduled visit 
rather than only reporting 
the lowest value across the 
duration of the study.
9.4.1 Safety analyses 
Text was added to state that data will be 
further presented by randomized dosing 
regimen. 
To reflect the change to 
weekly sc infusions.
9.6 Handling of dropouts 
or missing data 
Text was added to state that if individual 
platelet visit data is missing it will be set to 
zero; participants who are lost to follow-up 
will be imputed as nonresponders.
To clarify how missing 
platelet count data will be 
handled in the statistical 
analyses. 
9.7 Data monitoring
The 2-stage design and interim analysis 
was removed. 
To reflect the requirement 
to randomize a fixed 
number of participants on 
weekly sc infusions and 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 19 of 220
Section # and Name
Description of Change
Brief Rationale
removal of option to 
increase sample size based 
on an interim analysis.
9.7.1 Early stopping for 
efficacy 
9.7.2 Early stopping for 
futility 
Sections are no longer applicable. 
To reflect the requirement 
to randomize a fixed 
number of participants on 
weekly sc infusions and 
removal of option to 
increase sample size based 
on an interim analysis.
9.8 Determination of 
sample size
Table 9-3 Expected sample 
size for TP0003
The sample size calculation was updated. 
To reflect the requirement 
to randomize a fixed 
number of participants on 
weekly sc infusions and 
removal of option to 
increase sample size based 
on an interim analysis.
10.2 Appendix 2
Table 10-1 Protocol-
required safety laboratory 
assessments
Platelet reticulocytes and glycosylated 
hemoglobin were removed. Associated 
footnotes were removed. 
Updated to reflect that the 
analysis will not be 
performed. 
10.2 Appendix 2
Table 10-1 Protocol-
required safety laboratory 
assessments
Footnote a was updated from “sponsor” to 
“study participant”. 
Updated to correct an error.
10.4 Appendix 4: 
Contraceptive guidance 
and collection of 
pregnancy information
Footnote c has been removed from Table 
10-2.
To remain consistent with 
the Phase 3 
rozanolixizumab clinical 
program.
10.6 Appendix 6: Liver 
safety – suggested actions
and follow-up assessments
The cross reference to the liver chemistry 
stopping criteria was corrected in Table 10-
4. 
Corrected to reference the 
appropriate section of the 
protocol.
10.8, Appendix 8: 
Country-specific 
requirements
Poland 
Visit 29 was updated to Visit 28.
Updated to align with the 
updated Visit numbering.
10.8, Appendix 8: 
Country-specific 
requirements
Japan
The following text was deleted: 
“In reference to the overall design 
(Section 1 and Section 4.1), the following 
text has been added:
In the Phase I study, UP0060 (see 
Section 2.2), Japanese study participants 
have only been administered a maximum 
The 
 starting dose 
has been removed so this 
text no longer applies. 
Three Japanese study 
participants were observed 
while hospitalized under 
protocol amendment 2.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 20 of 220
Section # and Name
Description of Change
Brief Rationale
of 
rozanolixizumab sc, therefore 
the first 4 study participants in Japan will 
be observed whilst hospitalized for the first 
3 days (until Day 3) at a minimum after the 
starting dose.”
10.8, Appendix 8: 
Country-specific 
requirements
Japan
Exclusion criteria 20b (previously 20a) was 
updated based on the updates to the main 
criterion. 
Updated for consistency 
with changes introduced in 
exclusion criterion 20b.
10.8, Appendix 8: 
Country-specific 
requirements
Japan
Text pertaining to IGRA TB assessment 
and chest x-ray for TB was removed. 
Updated for consistency 
throughout the protocol
10.8, Appendix 8: 
Country-specific 
requirements
Japan
A cross reference was added to Table 10-2 
and the wording was updated.
Updated to provide clarity.
10.8, Appendix 8: 
Country-specific 
requirements
Japan
Wording of the definitions of AEs and 
SAEs was updated.
Updated to ensure 
consistency in the 
definitions for AEs and 
SAEs throughout the 
protocol.
10.9 Appendix 9: 
Abbreviations and 
trademarks
The definitions for the following 
abbreviations were added: COVID-19, 
LTBI, OPSI, QW, Q2W and RO. 
General update. 
10.11 Appendix 11: 
Karnofsky Performance 
Status Scale 
The Karnofsky Performance Status Scale 
was removed. 
Updated to ensure 
consistency with the 
removal of Exclusion 
Criterion 15.
10.22 Appendix 22: 
Management of Headaches 
The text was updated to clarify the 
management of IMP administration 
including dose adjustment following an AE 
of headache.
Updated to reflect the 
current general program 
guidance for the 
management of headaches
10.24 Appendix 24: 
Management of infusion 
reactions or 
hypersensitivity reactions
Additional text was added: “Fully trained 
healthcare professionals administering the 
IMP at home should follow their own 
management guidelines, which should be 
reviewed and endorsed by the investigator 
prior to first home administration.”
Updated for consistency.
10.24 Appendix 24: 
Management of infusion 
reactions or 
hypersensitivity reactions
Serum cytokines were removed. 
Blood cytokine sampling 
was removed as analysis of 
cytokines is not required in 
the ITP protocols as 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 21 of 220
Section # and Name
Description of Change
Brief Rationale
samples have been 
collected in other 
rozanolixizumab studies 
and no additional 
information is expected 
from the ITP population.
10.25 Appendix 25: 
Management of infections 
and 
hypogammaglobulinemia
The text was updated to clarify the 
management of IMP administration 
including dose adjustment following 
episodes of infections and 
hypogammaglobulinemia.
The total serum IgG cut-off 
value for informing the 
investigators has been 
aligned for all study 
participants based on the 
lack of conclusive literature 
supporting the previous 
approach. 
The investigators are given 
total flexibility in deciding 
if and how to continue the 
IMP treatment in cases of 
total IgG values <1g/L, 
based on a holistic 
approach of the study 
participant's status 
(platelets response, signs 
and symptoms of non-
serious/serious infection, 
potential risk of acquiring a 
non-serious/serious 
infection).
10.26 Appendix 26: 
Protocol Amendment 
History 
Protocol amendment 2 (global amendment) 
has been added. 
General update.
Throughout
Minor editorial and formatting changes 
have been made.
Minor, therefore have not 
been summarized.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 22 of 220
SERIOUS ADVERSE EVENT REPORTING
Serious adverse event reporting (24h)
All serious adverse events (SAEs) will be reported and transmitted to Patient 
Safety through the electronic Case Report Form (eCRF) system. The numbers 
below are to be used to send ancillary documentation only (eg, discharge 
summaries, death certificates) or in the event that the eCRF is not available.
Fax
Europe and Rest of the World: +32 2 386 24 21
US: +1 800 880 6949 or +1 866 890 3175
Email
Global (for interventional clinical studies): DS_ICT@ucb.com
Serious adverse event (investigational device) and 
device deficiency reporting (24h) 
Fax:
Japan: +81 3 6864 7400
Email:
Japan: UCBJ-Safety@ucb.com
COPY
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 23 of 220
TABLE OF CONTENTS
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE......................................2
SERIOUS ADVERSE EVENT REPORTING........................................................................22
1
PROTOCOL SUMMARY...............................................................................................29
1.1 Synopsis ...........................................................................................................................29
1.2 Schema.............................................................................................................................39
1.3 Schedule of activities .......................................................................................................40
2
INTRODUCTION ...........................................................................................................49
2.1 Study rationale .................................................................................................................49
2.2 Background......................................................................................................................51
2.3 Benefit/risk assessment....................................................................................................53
3
OBJECTIVES AND ENDPOINTS .................................................................................55
4
STUDY DESIGN.............................................................................................................59
4.1 Overall design ..................................................................................................................59
4.2 Scientific rationale for study design.................................................................................61
4.3 Justification for dose........................................................................................................62
4.4 End of study definition.....................................................................................................63
5
STUDY POPULATION ..................................................................................................64
5.1 Inclusion criteria ..............................................................................................................64
5.2 Exclusion criteria .............................................................................................................65
5.3 Lifestyle restrictions.........................................................................................................69
5.4 Screen failures..................................................................................................................70
6
STUDY TREATMENTS.................................................................................................71
6.1 Preparation, handling, storage, and accountability requirements ....................................71
6.1.1
Drug accountability .............................................................................................72
6.2 Measures to minimize bias: randomization and blinding ................................................72
6.2.1
Procedures for maintaining and breaking the treatment blind.............................73
6.2.1.1
Maintenance of study treatment blind.......................................................73
6.2.1.2
Breaking the treatment blind in an emergency situation...........................74
6.3 Treatment compliance......................................................................................................74
6.4 Concomitant medication(s)/treatment(s)..........................................................................75
6.4.1
Permitted concomitant treatments (medications and therapies) ..........................75
6.4.2
Prohibited concomitant treatments (medications and therapies) .........................75
6.4.3
Rescue therapy.....................................................................................................76
6.5 Dose modification............................................................................................................77
6.6 Treatment after the end of the study ................................................................................77
7
DISCONTINUATION OF IMP AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL........................................................................78
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 24 of 220
7.1 Discontinuation of IMP....................................................................................................78
7.1.1
Liver chemistry stopping criteria.........................................................................78
7.1.2
QTc stopping criteria ...........................................................................................79
7.1.3
Discontinuation of IMP due to other adverse events or medical condition.........80
7.1.4
Temporary IMP discontinuation..........................................................................80
7.2 Participant discontinuation/withdrawal from the study ...................................................81
7.3 Lost to follow up..............................................................................................................82
8
STUDY ASSESSMENTS AND PROCEDURES...........................................................83
8.1 Efficacy assessments........................................................................................................84
8.1.1
Platelet counts......................................................................................................84
8.1.2
ITP bleeding score ...............................................................................................86
8.1.3
Patient Reported Outcomes .................................................................................86
8.1.3.1
ITP-PAQ....................................................................................................86
8.1.3.2
SF-36 .........................................................................................................87
8.1.3.3
FATIGUE-PRO Physical Fatigue Scale....................................................87
8.1.3.4
EQ-5D-5L..................................................................................................87
8.1.3.5
PGI-S.........................................................................................................87
8.1.3.6
PGI-C.........................................................................................................87
8.2 Safety assessments...........................................................................................................88
8.2.1
Physical examination...........................................................................................88
8.2.2
Vital signs ............................................................................................................88
8.2.3
Electrocardiograms..............................................................................................88
8.2.4
Clinical safety laboratory assessments ................................................................89
8.2.5
Assessment and management of TB and TB risk factors....................................89
8.2.5.1
Tuberculosis assessment............................................................................89
8.2.5.2
Tuberculosis management.........................................................................90
8.2.6
Splenectomized study participants ......................................................................91
8.3 Adverse events.................................................................................................................92
8.3.1
Time period and frequency for collecting AE and SAE information..................92
8.3.2
Method of detecting AEs and SAEs ....................................................................92
8.3.3
Follow-up of AEs and SAEs................................................................................92
8.3.4
Regulatory reporting requirements for SAEs ......................................................93
8.3.5
Pregnancy ............................................................................................................93
8.3.6
Anticipated serious adverse events......................................................................93
8.3.7
Adverse events of special interest........................................................................94
8.3.8
Adverse events of special monitoring..................................................................94
8.3.9
Treatment-emergent adverse events ....................................................................94
8.3.10
COVID-19 vaccination........................................................................................95
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03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 25 of 220
8.4 Safety signal detection .....................................................................................................95
8.5 Treatment of overdose .....................................................................................................95
8.6 Pharmacokinetics and antidrug antibodies.......................................................................96
8.7 Pharmacodynamics ..........................................................................................................96
8.8 Genetics............................................................................................................................96
8.8.1
Pharmacogenomics..............................................................................................96
8.8.2
Immunology.........................................................................................................97
8.9 Exploratory biomarkers ...................................................................................................97
8.10 Medical resource utilization and health economics .........................................................98
9
STATISTICAL CONSIDERATIONS.............................................................................99
9.1 Definition of analysis sets................................................................................................99
9.2 General statistical considerations.....................................................................................99
9.3 Planned efficacy/outcome analyses ...............................................................................100
9.3.1
Analysis of the primary efficacy/primary endpoint...........................................100
9.3.2
Analysis of the secondary efficacy endpoints ...................................................104
9.3.3
Other efficacy/other outcome analyses..............................................................110
9.3.3.1
Analysis of pharmacokinetic endpoint ....................................................110
9.3.3.2
Antidrug antibodies analyses...................................................................110
9.3.3.3
Analysis of pharmacodynamic endpoints................................................110
9.4 Planned safety and other analyses..................................................................................111
9.4.1
Safety analyses...................................................................................................111
9.5 Handling of protocol deviations.....................................................................................111
9.6 Handling of dropouts or missing data............................................................................111
9.7 Data monitoring .............................................................................................................111
9.7.1
Early stopping for efficacy ................................................................................112
9.7.2
Early stopping for futility ..................................................................................112
9.8 Determination of sample size.........................................................................................112
10
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS.114
10.1 Appendix 1: Regulatory, ethical, and study oversight considerations...........................114
10.1.1
Regulatory and ethical considerations...............................................................114
10.1.2
Financial disclosure ...........................................................................................114
10.1.3
Informed consent process ..................................................................................115
10.1.4
Data protection...................................................................................................115
10.1.5
Committees structure.........................................................................................116
10.1.6
Data quality assurance .......................................................................................116
10.1.6.1
Electronic Case Report Form completion ...............................................116
10.1.6.2
Apps.........................................................................................................117
10.1.7
Source documents..............................................................................................117
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03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 26 of 220
10.1.8
Study and site closure ........................................................................................117
10.1.9
Publication policy..............................................................................................118
10.2 Appendix 2: Clinical laboratory tests ............................................................................119
10.3 Appendix 3: Adverse events – definitions and procedures for recording, evaluating, 
follow up, and reporting.................................................................................................121
10.3.1
Definition of AE ................................................................................................121
10.3.2
Definition of SAE..............................................................................................122
10.3.3
Recording and Follow up of AE and/or SAE ....................................................124
10.3.4
Reporting of SAEs.............................................................................................126
10.4 Appendix 4: Contraceptive guidance and collection of pregnancy information ...........127
10.5 Appendix 5: Genetics.....................................................................................................130
10.6 Appendix 6: Liver safety – suggested actions and follow-up assessments ...................131
10.7 Appendix 7: Medical device incidents – definition and procedures for recording, 
evaluating, follow up, and reporting..............................................................................135
10.8 Appendix 8: Country-specific requirements..................................................................136
Medical Device – Adverse events (ADEs, SAEs, and SADEs) and device deficiencies..138
Definition of AE and ADE ................................................................................................139
Definition of SAE, and SADE...........................................................................................140
Definition of Device Deficiency........................................................................................141
Recording and Follow-Up of AE and/or SAE and Device Deficiencies...........................141
Reporting of SAEs.............................................................................................................142
Reporting of SADEs ..........................................................................................................142
Reporting of AE and/or Device Deficiencies ....................................................................142
10.9 Appendix 9: Abbreviations and trademarks ..................................................................143
10.10
Appendix 10: Rapid alert procedures ..................................................................147
10.11
Appendix 11: Karnofsky Performance Status Scale............................................148
10.12
Appendix 12: ITP-BAT .......................................................................................149
10.13
Appendix 13: ITP-PAQ .......................................................................................157
10.14
Appendix 14: SF-36 Form ...................................................................................168
10.15
Appendix 15: FATIGUE-PRO Physical Fatigue Scale .......................................173
10.16
Appendix 16: EQ-5D-5L .....................................................................................174
10.17
Appendix 17: PGI-S.............................................................................................176
10.18
Appendix 18: PGI-C ............................................................................................177
10.19
Appendix 19: Tuberculosis assessment ...............................................................178
10.20
Appendix 20: Headache questionnaire ................................................................179
10.21
Appendix 21: Sampson Criteria Questionnaire ...................................................183
10.22
Appendix 22: Management of headaches............................................................184
10.23
Appendix 23: Management of diarrhea ...............................................................186
10.24
Appendix 24: Management of infusion reactions or hypersensitivity reactions..187
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 27 of 220
10.25
Appendix 25: Management of infections and hypogammaglobulinemia............189
Dose adjustments/mock infusions .....................................................................................190
Splenectomized study participants.....................................................................................190
10.26
Appendix 26: Protocol Amendment History .......................................................192
11
REFERENCES ..............................................................................................................218
SPONSOR DECLARATION................................................................................................220
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
220
iza
220
application and any extensions or variations thereof. 


UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 28 of 220
LIST OF TABLES
Table 1-1:
Dose adjustments of IMP following initial dose..............................................35
Table 1-2:
TP0003 dose levels and weight tiers of IMP ...................................................38
Table 1-3:
Schedule of activities (Prolonged Screening only for splenectomized 
study participants)............................................................................................40
Table 1-4:
Schedule of activities.......................................................................................41
Table 3-1:
Study objectives and endpoints........................................................................55
Table 5-1:
Treatment-free periods for immunosuppressants, biologics, other 
therapies, and antiplatelet/anticoagulant agents...............................................67
Table 6-1:
Treatments administered..................................................................................71
Table 6-2:
Permitted concomitant treatments (medications and therapies) ......................75
Table 8-1:
Anticipated serious adverse events for ITP population ...................................93
Table 9-1:
Estimands for the primary endpoint...............................................................101
Table 9-2:
Estimands for secondary endpoints ...............................................................105
Table 9-3: Expected sample size for TP0003 ........................................................................112
Table 10-1:
Protocol-required safety laboratory assessments...........................................119
Table 10-2:
Highly effective contraceptive methodsa .......................................................128
Table 10-3:
Phase 3-4 liver chemistry stopping criteria and follow-up assessments........132
Table 10-4:
Phase 3-4 liver chemistry increased monitoring criteria with continued 
IMP ................................................................................................................134
Table 10-5:
ITP-Bleeding Assessment Tool .....................................................................149
Table 10-6:
Headache Questionnaire ................................................................................179
Table 10-7:
Suggested management guidelines at the study site for infusion reactions...187
Table 10-8:
Management of infections and hypogammaglobulinemia.............................190
LIST OF FIGURES
Figure 1-1:
TP0003 dose adjustments of IMP....................................................................36
Figure 1-2:
TP0003 study schematic ..................................................................................39
Figure 7-1:
Liver chemistry stopping criteria and increased monitoring algorithm...........78
Figure 7-2:
Liver chemistry increased monitoring algorithm with continued study 
intervention for participants with ALT ≥3xULN but <8xULN.......................79
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 29 of 220
1
PROTOCOL SUMMARY
1.1
Synopsis
Protocol title
A Phase 3 Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the 
Efficacy, Safety, and Tolerability of Rozanolixizumab in Adult Study Participants with 
Persistent or Chronic Primary Immune Thrombocytopenia (ITP)
Short title
A Phase 3 study evaluating the efficacy, safety, and tolerability of rozanolixizumab in adult 
study participants with ITP
Rationale
Immune thrombocytopenia is a clinical disorder in which thrombocytopenia manifests as a 
bleeding tendency, purpura, or petechiae. Autoantibodies against platelet antigens are considered 
to be a hallmark of ITP. Production of pathogenic immunoglobulin (Ig) G autoantibodies by 
plasma cells is accepted as the central underlying pathophysiological mechanism in a number of 
IgG-mediated autoimmune diseases, which includes ITP. In some patients, antibodies recognize 
antigens derived from a single glycoprotein; whereas in others, antibodies recognize multiple 
glycoproteins. The spleen is the key organ in the pathophysiology of ITP, not only because 
platelet autoantibodies are formed in the white pulp, but also because mononuclear macrophages 
in the red pulp destroy immunoglobulin-coated platelets.
Treatments aimed at reducing the quantity of circulating IgG autoantibodies are being used for 
primary and secondary therapy of autoimmune diseases including ITP, particularly where 
corticosteroid-based immune suppression is not or no longer effective. The therapeutic approach 
of these treatments is based on lowering levels of pathogenic autoantibodies, which represents 
rational and effective treatment modalities of autoimmune diseases. The primary goal for 
treatment of ITP is to achieve a platelet count that prevents major bleeding, rather than correcting 
the platelet count to normal levels.
Rozanolixizumab is a humanized IgG4P monoclonal antibody that is being developed as an 
inhibitor of the activity of neonatal Fc receptor (FcRn). The FcRn receptor recycles IgG and 
albumin and transports it bidirectionally across epithelial barriers. Recent studies have shown 
that FcRn rescues both IgG and albumin from intracellular lysosomal degradation by recycling it 
from the sorting endosome to the cell surface (Anderson et al, 2006). Rozanolixizumab has been 
specifically designed to block IgG binding to FcRn without blocking the binding and recycling 
of albumin. By blocking the activity of FcRn, rozanolixizumab accelerates the catabolism of IgG 
antibodies, including IgG autoantibodies. This Phase 3 study, TP0003, will be one of 2 studies 
that will provide the required data to establish the efficacy and safety of rozanolixizumab over 
placebo in study participants with persistent or chronic primary ITP who have failed or were 
intolerant to two or more prior ITP therapy and who require an increase and sustained effect in 
their platelet counts.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 30 of 220
Objectives and endpoints
Objectives
Endpoints
Primary
•
To demonstrate the clinical efficacy of 
rozanolixizumab in maintenance treatment 
in study participants with primary ITP
The primary efficacy endpoint is:
•
Durable Clinically Meaningful Platelet 
Response of ≥50×109/L, for at least 8 out 
of 12 weeks during the last 12 weeks 
(Week 13 to 25)
The secondary efficacy endpoints are:
•
Cumulative number of weeks with 
Clinically Meaningful Platelet Response 
of ≥50×109/L over the 24-week treatment 
period
•
Time to first Clinically Meaningful 
Platelet Response of ≥50×109/L: time 
from starting treatment to achievement of 
first response of ≥50×109/L 
•
Clinically Meaningful Platelet Response 
of ≥50×109/L by Day 8
•
Response defined as platelet count 
≥30×109/L and at least a 2-fold increase 
of the Baseline count confirmed on at 
least 2 separate occasions at two adjacent 
nominal visits at least 7 days apart, and 
absence of bleeding by visit a,b
•
Time to first rescue therapy
•
Change from Baseline to Week 25, in ITP 
Patient Assessment Questionnaire 
(ITP-PAQ) Symptoms Score
The other efficacy endpoints are:
•
Duration of first Clinically Meaningful 
Platelet Response of ≥50×109/L: 
measured from achievement of first 
Response to loss of first Response (loss of 
Response defined as platelet count 
<50×109/L)
•
Time to first Response: time from starting 
treatment to achievement of Response 
•
Usage of rescue therapy by visit
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 31 of 220
•
Complete Response defined as platelet 
count ≥100×109/L confirmed on at least 
2 separate occasions at two adjacent 
nominal visits at least 7 days apart, and 
absence of bleeding by visit a,b
•
Cumulative number of weeks over the 
planned 24-week treatment period with 
platelet count of ≥100×109/L.
•
Cumulative number of weeks over the 
planned 24-week treatment period with 
platelet counts ≥30×109/L and at least 
doubling from Baseline.
•
Mean change from Baseline in platelet 
count by visit.
•
Clinically Meaningful Platelet Response 
of ≥50×109/L, for at least 4 out of 6 weeks 
during the last 6 weeks (Week 19 to 25).
•
Clinically Meaningful Platelet Response 
of ≥50×109/L, for at least 6 out of 8 weeks 
during the last 8 weeks (Week 17 to 25).
Secondary
•
To assess the safety and tolerability of 
rozanolixizumab
The safety endpoints are:
•
Occurrence of treatment-emergent adverse 
events (TEAEs)
•
Occurrence of TEAEs leading to 
withdrawal of investigational medicinal 
product (IMP) (ie, study discontinuation)
The other safety endpoints are:
•
Occurrence of serious TEAEs
•
Occurrence of treatment related TEAEs
•
Occurrence of adverse events of special 
monitoring (AESM)
•
Vital signs change from Baseline (blood 
pressure [BP], pulse rate, body 
temperature) at each scheduled 
assessment during Treatment and Safety 
Follow-up (SFU) Periods
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 32 of 220
•
12-lead electrocardiogram (ECG) change 
from Baseline at each scheduled ECG 
visit 
•
Laboratory change from Baseline 
(hematology including coagulation 
parameters, clinical chemistry, and 
urinalysis) at each scheduled assessment 
during Treatment and SFU Periods
•
Change from Baseline in concentrations 
of total protein and albumin
•
Change from Baseline in serum 
complement levels (C3 and C4) and 
plasma complement levels (C3a and C5a) 
at each scheduled assessment during the 
study (for study participants experiencing 
infusion reactions or hypersensitivity 
reactions)
Exploratory 
•
To evaluate the clinical efficacy as 
measured by the ITP bleeding score
•
ITP-specific Bleeding Assessment Tool 
(ITP-BAT) bleeding events and severity 
by visit
•
To assess the effect of rozanolixizumab 
on health-related quality of life (HRQoL)
•
Change from Baseline in European 
Quality of Life (EuroQol) -5 dimension 5 
Levels (EQ-5D-5L) item responses
•
Change from Baseline in Short form 
36-item (SF-36) domain and composite 
scores 
•
Change from Baseline in the ITP-PAQ 
domain scores
•
To assess hospitalizations due to ITP
•
Number and length of hospitalizations
•
To assess the effect of rozanolixizumab 
on patient reported outcomes (PROs)
•
Change from Baseline in FATIGUE-PRO 
Physical Fatigue Score
•
Change from Baseline in Patient Global 
Impression of Severity (PGI-S)
•
Patient Global Impression of Change 
(PGI-C) at all available post-baseline 
assessments
•
To assess the pharmacokinetics of 
rozanolixizumab administered by 
subcutaneous (sc) infusion
•
Plasma concentration of rozanolixizumab 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 33 of 220
•
To evaluate the incidence and emergence 
of antidrug antibodies (ADAs) of 
rozanolixizumab
•
ADAs at each scheduled assessment 
•
To assess the pharmacodynamic (PD) 
effects of rozanolixizumab
The exploratory PD endpoints are:
•
Total serum IgG (absolute value) and 
change from Baseline (absolute value and 
percentage) in serum IgG and in serum 
IgG subclass concentration at each 
scheduled assessment 
•
Absolute values and change from 
Baseline (absolute value and percentage)
in serum immunoglobulin concentrations 
(IgA, IgE, IgM) at each scheduled 
assessment 
•
To assess the influence of 
rozanolixizumab treatment on vaccination 
titers
•
Percent change from Baseline in 
vaccination titers against Streptococcus 
pneumoniae, Neisseria meningitidis, and 
Haemophilus influenzae in 
splenectomized study participants
•
Percent change from Baseline in 
vaccination titers against tetanus in all 
study participants
•
To assess the effect of rozanolixizumab 
on response to vaccination in study 
participants who received COVID-19 
vaccine
•
Change in biomarkers of COVID-19 
vaccine response over time
a Absence of bleeding indicated by Grade 0 for all domains of the skin, mucosae, and organs (SMOG), or a Skin 
Grade of 0 or 1.
b Nominal visits are on-site visits where ITP bleeding scale assessment is performed.
Overall design
This is a Phase 3, multicenter, double-blind, randomized, placebo-controlled study with 
rozanolixizumab in study participants with persistent or chronic primary ITP defined as more 
than 3 months, or more than 12 months of duration respectively, since diagnosis.
The study participants will be male and female adults with persistent or chronic primary ITP, 
history of prior ITP treatment, a platelet count measurement at Screening (Visit 1) and at 
Baseline with an average of the two <30×109/L (no single count may be >35×109/L) and a 
documented history of low platelet count (<30×109/L) any time prior to Screening.
Participants should previously have received two or more ITP therapies and should have initially 
responded to such therapy and have a current or history of a blood smear consistent with primary 
ITP.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 34 of 220
Study participants who have previously undergone a splenectomy will be included in the study 
provided they do not meet the protocol defined exclusion criteria (Section 5.2) in order to 
optimize protection against overwhelming post-splenectomy infection (OPSI). Splenectomized 
study participants should be vaccinated against the encapsulated organisms, such as 
Streptococcus pneumoniae (S. pneumoniae), Neisseria meningitidis (N. meningitidis), and 
Haemophilus influenzae (H. influenzae) (as per local/or national guidance, as applicable) as 
evidenced from immunization records or during the Prolonged Screening Period. Study 
participants, who are due to receive a booster, can be screened after they received the required 
booster. 
Splenectomized study participants will be required to attend a Prolonged Screening Period prior 
to the Screening Visit to receive, if applicable, the required vaccinations (see Table 1-3). 
The study will assess whether multiple sc infusions of rozanolixizumab will result in a durable 
Clinically Meaningful Platelet Count of ≥50×109/L, for at least 8 out of 12 weeks during the last 
12 weeks of the Treatment Period (Weeks 13 to 25). Starting at Week 2, platelet counts will be 
measured every week at a local laboratory. Home visits including home dosing and assessments 
as per Section 1.3 can be conducted once all pre-requisites for a home dosing visit are fulfilled. 
Once eligibility is confirmed on Day 1 (Baseline Visit), study participants will enter the 
Treatment Period (24 weeks) and will be randomized 2:1 to receive a fixed-unit dose of 
rozanolixizumab equivalent to 
 or placebo once a week (QW) with randomization 
stratified by the degree of thrombocytopenia (platelet count < or ≥15×109/L) and history of 
splenectomy (yes or no). The last assessment of the Treatment Period will take place at Week 25.
During the first 12 weeks in the study (Week 1 until Week 12) IMP dose adaptations, depending 
on the observed levels of platelets as detailed in Table 1-1, will be allowed. The Dose Adaptation 
Period aims at achieving an IMP dose regimen that sustains a platelet count ≥50×109/L to 
≤150×109/L until the beginning of Week 13. Following the initial dose equivalent to 
, 
subsequent QW doses can be adapted to dose equivalents to 
 QW or 
 total dose 
(corresponding to an average 
dose in a participant weighing 70kg) QW based on the 
platelet count. Following this Dose Adaptation Period, study participants will enter the 
Maintenance Period starting at Week 13 until Week 25. The dose regimen that achieves platelet
stabilization in the adaptation period will be continued throughout the Maintenance Period. 
During the Maintenance Period the dose regimen should remain stable and further dose 
adaptations should be avoided if possible. However, adjustments for safety and efficacy reasons 
will still be allowed as outlined in Table 1-1 and Figure 1-1, which presents the dose titration for 
IMP based on the platelet count. 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 35 of 220
Table 1-1:
Dose adjustments of IMP following initial dose
Platelet count resulta
Dose adjustment (based on weekly platelet counts)
<10×109/L 
Rescue therapy is highly recommended as per 
Section 6.4.3. 
≥10×109/L to <30×109/L (on at least two 
consecutive visits)
Rescue therapy is recommended as per Section 6.4.3.
≥30×109/L to <50×109/L
(on at least two consecutive visits)
Increase by one dose level, unless study participant is on 
maintenance dose of 
≥50×109/L to ≤150×109/Lb
Continue with current dose level
>150×109/L to <400×109/L (on at least 
two consecutive visits)
Decrease by one dose level, unless study participant is on 
maintenance dose of 
≥400×109/L
Stop IMP treatment.
Once the platelet count is ≤150×109/L, reinitiate treatment 
decreased by one dose level 
a All analyses of platelet counts will be based on local laboratory results
b Due to the interindividual variable platelet response, in some study participants platelet count may abruptly fall 
below 50×109/L after dose reduction or treatment discontinuation. In these cases, if clinically appropriate, higher 
cut-off levels of platelet count for dose reduction (>150×109/L) may be considered according to medical 
judgment, but should not exceed 250×109/L.
For the dose adjustments where a decrease is required, study participants receiving 
 
should continue at this dose level, as dose reductions below 
 are not applicable. If a study 
participant is in the lowest body weight tier (below 50kg) and is on the lowest dose level with a 
platelet count between >150×109/L and <400×109/L, the investigator might decide to temporarily 
stop treatment according to medical judgment based on the observation of platelet variability. If 
the platelet count increases to above 400×109/L, then IMP must be stopped.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 36 of 220
Figure 1-1:
TP0003 dose adjustments of IMP
eqv=equivalent; QW=once a week
Dose adaptations may start as early as Week 2
* eqv: fixed-unit dose with body weight tiers equivalent to the mg/kg dose in terms of IgG reductions and safety 
profile
If treatment as per Table 1-1 and Figure 1-1 does not lead to an increase in platelet count 
≥30×109/L, the study participant can be treated with rescue therapy, if deemed needed by the 
investigator. If platelet count is ≥10×109/L to <30×109/L or active bleeding, rescue therapy is 
recommended (eg, commercially available medication, such as intravenous immunoglobulin 
[IVIg], high dose corticosteroids and pulse steroids, platelet transfusions, or any other 
medication listed in Section 6.4.3). If platelet count is <10×109/L, rescue therapy is highly 
recommended as per Section 6.4.3. If a study participant has been down-titrated to a fixed-unit 
dose equivalent to 
 total dose (corresponding to an 
 dose in 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 37 of 220
a participant weighing 70kg), and platelet count decreases to less than 50×109/L, then up-titration 
to a fixed-unit dose equivalent to 
 QW or 
 QW, respectively, would be allowed.
Study participants should be monitored for signs of arterial or venous thrombotic and 
thromboembolic events. If such events occur, the investigator should undertake the appropriate 
management per medical judgment and local guidance, and contact the Medical Monitor. 
Thrombotic or embolic events are considered AESM, as described in Section 8.3.8, and the 
reporting rules can be found in Appendix 3, Section 10.3.
All study participants completing the Treatment Period (regardless of whether they received 
rescue therapy or not) and fulfilling the open-label extension (OLE) study (TP0004) eligibility 
criteria will be allowed to enroll into the 1-year OLE treatment study TP0004. The enrollment 
into the TP0004 study should be conducted on the same day as Visit 27 (Week 25) of the feeder 
study. In case the enrollment into TP0004 is not conducted at Week 25 (Visit 27), a visit window 
of +3 days will be granted; therefore, rollover needs to be completed 3 days after Week 25 at the 
latest.
Participants that will not be enrolling into the OLE study will be followed for up for 8 weeks 
after the last administration of IMP. The End of Study (EOS) Visit will be performed after the 
SFU Period.
An external Independent Data Monitoring Committee (IDMC) will be established to review the 
safety data at predefined intervals and ad hoc as needed should emerging safety concerns arise 
during the study. The first IDMC meeting for the review of safety data is planned to occur after 
approximately 15 participants have received 3 doses of IMP in TP0003. The study will be put on 
hold if any of the following occurs
•
The IDMC judges it necessary for medical or safety reasons and
•
The sponsor or its designee judges it necessary for medical, safety, regulatory, or any other 
reasons consistent with applicable laws, regulations and Good Clinical Practice.
•
Three study participants experience any serious adverse event (SAE) of the same type within 
the first 15 study participants who have received 3 doses of IMP across TP0003 and TP0006, 
unless the SAE is clearly unrelated to the study drug.
−
For US and Canada only: Three study participants experience any SAE within the first 
15 study participants who have received at least one dose of IMP across TP0003 and 
TP0006, unless the SAE is clearly unrelated to the study drug.
It is intended to have one IDMC for both of the pivotal studies (TP0003 and TP0006), where the 
safety data will be initially presented unpooled, ie, data from each study will be reviewed 
separately. Key safety data may be pooled at the discretion of the IDMC for protection of all 
study participants if warranted. 
Based on feedback from the IDMC, weekly dosing was implemented in protocol amendment 3. 
Study participants being treated with the bi-weekly dosing regimen will switch to the weekly 
dosing regimen once protocol amendment 3 is approved at the respective study site. 
Additionally, the sponsor's Safety Signal Detection Team will perform aggregated safety data 
reviews at predefined intervals across all rozanolixizumab programs.
For Japan specific regulations, see Appendix 8, Section 10.8.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 38 of 220
Number of participants
Study participants will be randomly assigned to IMP in a 2:1 ratio to either rozanolixizumab or 
placebo, respectively. The total sample size will be approximately 90 study participants, at least 
60 of which will be randomized to weekly IMP administration (for determination of sample size,
see Section 9.8).
Treatment groups and duration
The total maximum study duration per study participant is up to 35 weeks, consisting of a 
Screening Period (up to 4 weeks), a Dose Adaptation Period (12 weeks), a Maintenance Period 
(12 weeks) and a SFU Period (8 weeks after final dose administered). The eligibility of study 
participants to participate in the study will be determined during the Screening Period (Day -28 
to Day -1). Splenectomized participants will be required to attend a Prolonged Screening Period 
prior to the Screening Visit to assess and receive, if applicable, the required vaccinations, which 
will extend the total study duration by up to 20 weeks.
Fixed-unit doses across body weight tiers and treatment arms will be employed in this study 
according to the following scheme, as presented in Table 1-2.
Table 1-2:
TP0003 dose levels and weight tiers of IMP
Dose* eqv
Bodyweight
Dose level 1
Dose level 2
Dose level 3
>35 to <50kg
No weight adjustment  
≥50 to <70kg
≥70 to <100kg
≥100kg
eqv=equivalent; IMP=investigational medicinal product 
If a study participant is in the lowest body weight tier (below 50kg) and is on the lowest dose level with 
a platelet count between >150×109/L and <400×109/L, the investigator might decide to temporarily stop 
treatment according to medical judgment based on the observation of platelet variability. If the platelet 
count increases above 400×109/L then treatment must be stopped anyway.
The placebo arm will use 0.9% sodium chloride aqueous solution (physiological saline, 
preservative free) for sc administration, matching the volumes of the rozanolixizumab arm.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 39 of 220
1.2
Schema
A schematic diagram of the study is presented in Figure 1-2.
Figure 1-2:
TP0003 study schematic
QW=once a week; SFU=safety follow-up
Platelet counts will be measured weekly at local laboratories.
Splenectomized participants would need to attend a Prolonged Screening Period for up to 20 weeks prior to the 
Screening Visit.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 40 of 220
1.3
Schedule of activities
The Schedule of Activities for TP0003 is presented in Table 1-3 (specific for splenectomized 
study participants) and Table 1-4 (for all study participants).
Table 1-3:
Schedule of activities (Prolonged Screening only for 
splenectomized study participants) 
Assessments
Prolonged Screening 
Visit Part 1a
Prolonged Screening 
Visit Part 2
Visit
1.1
Additional visits may be 
required depending on the 
vaccine and on the vaccination 
history 
1.2
Week
-20
-20 to -8
-4 to -1
Day
-140
-140 to -56
-28 to -1
Visit 
Window
±14d
±14d
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consent (for participating study participants)
X
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assessments of Visit 1 
as outlined in 
Table 1-4, including 
the Platelet counts 
(using site's local 
laboratory)
General medical/procedures history
X
Vaccinationb, c
X
X
ITP=primary immune thrombocytopenia
a Inclusion criterion #8 is not applicable to the Prolonged Screening Period (Visit Part 1). Study participants may 
take ITP concomitant medication as per Table 6-2.
b Administer vaccines to splenectomized participants without previous vaccination history for S. pneumoniae, 
H. influenzae and N. meningitidis, or as applicable as per local guidance, eg in Japan. 
c Administer vaccines to splenectomized participants who require a booster protection against S. pneumoniae, 
H. influenzae, and N. meningitidis or as applicable as per local guidance, eg in Japan. 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 41 of 220
Table 1-4:
Schedule of activities
Screening 
Period
Do
se
Treatment Period
SFU Period
Visit(s)
1
BL
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3
4
5
6
7
8, 10, 
12,14, 16, 
18, 20, 22, 
24
9, 13, 17, 
21, 25
11, 15, 19, 
23
26
27
28
29
EW
EOS
b, c
Week
-4 to -1
1
1
2
3
4
5
6, 8, 10, 
12, 14, 
16, 18, 
20, 22
7, 11, 15, 
19, 23
9, 13, 17, 
21
24
25
28
32
Day
-28 to -1
1
3
8
15
22
29
36, 50, 
64, 78, 
92, 106, 
120, 134, 
148
43, 71, 
99, 127, 
155
57, 85, 
113, 141
162
169
190
218
Assessmentsa
Visit
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+2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
Written informed consent 
and written 
pharmacogenomics substudy 
informed consent (for 
participating study 
participants)
X
Xe
Verification of 
inclusion/exclusion criteria
X
X
Demographic data
X
General medical/procedures 
history
X
ITP history
X
Prior and concomitant 
medication
X
X
X
X
X
X
X
X
X
X
X
X
X
X
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 42 of 220
Screening 
Period
Do
se
Treatment Period
SFU Period
Visit(s)
1
BL
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3
4
5
6
7
8, 10, 
12,14, 16, 
18, 20, 22, 
24
9, 13, 17, 
21, 25
11, 15, 19, 
23
26
27
28
29
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EOS
b, c
Week
-4 to -1
1
1
2
3
4
5
6, 8, 10, 
12, 14, 
16, 18, 
20, 22
7, 11, 15, 
19, 23
9, 13, 17, 
21
24
25
28
32
Day
-28 to -1
1
3
8
15
22
29
36, 50, 
64, 78, 
92, 106, 
120, 134, 
148
43, 71, 
99, 127, 
155
57, 85, 
113, 141
162
169
190
218
Assessmentsa
Visit
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+2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
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Concomitant medical 
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X
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X
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X
X
X
X
X
X
X
Serum pregnancy test
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X
X
X
X
X
X
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X
X
X
X
X
Body weight
X
X
Height
X
Recording of AEs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Full physical examination
X
X
X
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 43 of 220
Screening 
Period
Do
se
Treatment Period
SFU Period
Visit(s)
1
BL
/2
3
4
5
6
7
8, 10, 
12,14, 16, 
18, 20, 22, 
24
9, 13, 17, 
21, 25
11, 15, 19, 
23
26
27
28
29
EW
EOS
b, c
Week
-4 to -1
1
1
2
3
4
5
6, 8, 10, 
12, 14, 
16, 18, 
20, 22
7, 11, 15, 
19, 23
9, 13, 17, 
21
24
25
28
32
Day
-28 to -1
1
3
8
15
22
29
36, 50, 
64, 78, 
92, 106, 
120, 134, 
148
43, 71, 
99, 127, 
155
57, 85, 
113, 141
162
169
190
218
Assessmentsa
Visit
Windowc
+2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
Short physical examination
X
X
X
X
X
12-lead ECGj
X
X
X
Laboratory parameters 
(hematology, clinical 
chemistry, and urinalysis)
X
X
X
X
X
X
X
X
Serology test for HIV, 
hepatitis B, and hepatitis C
X
Vaccination titers
(in splenectomized 
participants)k
X
X
X
X
Tetanus titerl
X
X
X
X
COVID-19 biomarkers 
sampling (in participants 
vaccinated prior to entry into 
TP0003)m
X
X
X
PUBLIC COPY 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 44 of 220
Screening 
Period
Do
se
Treatment Period
SFU Period
Visit(s)
1
BL
/2
3
4
5
6
7
8, 10, 
12,14, 16, 
18, 20, 22, 
24
9, 13, 17, 
21, 25
11, 15, 19, 
23
26
27
28
29
EW
EOS
b, c
Week
-4 to -1
1
1
2
3
4
5
6, 8, 10, 
12, 14, 
16, 18, 
20, 22
7, 11, 15, 
19, 23
9, 13, 17, 
21
24
25
28
32
Day
-28 to -1
1
3
8
15
22
29
36, 50, 
64, 78, 
92, 106, 
120, 134, 
148
43, 71, 
99, 127, 
155
57, 85, 
113, 141
162
169
190
218
Assessmentsa
Visit
Windowc
+2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
COVID-19 biomarkers 
sampling (in participants 
vaccinated during TP0003)
Xn
X
TB signs and symptoms 
questionnaireo
X
X
X 
W13 only
X
X
Call to IRT for treatment kit 
number
X
X
X
X
X
X
X
X
X
Administration of IMPp
X
X
X
X
X
X
X
X
X
Blood sampling for plasma 
concentration of 
rozanolixizumabq
X
X
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X
Xr
all predose 
and 1 to 5 
days 
postdose 
after W13 
only
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 45 of 220
Screening 
Period
Do
se
Treatment Period
SFU Period
Visit(s)
1
BL
/2
3
4
5
6
7
8, 10, 
12,14, 16, 
18, 20, 22, 
24
9, 13, 17, 
21, 25
11, 15, 19, 
23
26
27
28
29
EW
EOS
b, c
Week
-4 to -1
1
1
2
3
4
5
6, 8, 10, 
12, 14, 
16, 18, 
20, 22
7, 11, 15, 
19, 23
9, 13, 17, 
21
24
25
28
32
Day
-28 to -1
1
3
8
15
22
29
36, 50, 
64, 78, 
92, 106, 
120, 134, 
148
43, 71, 
99, 127, 
155
57, 85, 
113, 141
162
169
190
218
Assessmentsa
Visit
Windowc
+2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
Anti-rozanolixizumab 
antibodiesq
X
X
X
X
Xr
all predose 
and 1 to 5 
days 
postdose 
after W13 
only
X
X
Serum complements (C3 and 
C4)s
X
X
Plasma complements (C3a 
and C5as
X
X
Whole blood collection for 
DNAt
X
X
Whole blood collection for 
RNAt
X
X
Blood collection for 
exploratory biomarkersu
X
X
PUBLIC COPY 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 46 of 220
Screening 
Period
Do
se
Treatment Period
SFU Period
Visit(s)
1
BL
/2
3
4
5
6
7
8, 10, 
12,14, 16, 
18, 20, 22, 
24
9, 13, 17, 
21, 25
11, 15, 19, 
23
26
27
28
29
EW
EOS
b, c
Week
-4 to -1
1
1
2
3
4
5
6, 8, 10, 
12, 14, 
16, 18, 
20, 22
7, 11, 15, 
19, 23
9, 13, 17, 
21
24
25
28
32
Day
-28 to -1
1
3
8
15
22
29
36, 50, 
64, 78, 
92, 106, 
120, 134, 
148
43, 71, 
99, 127, 
155
57, 85, 
113, 141
162
169
190
218
Assessmentsa
Visit
Windowc
+2dd
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±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
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Immunoglobulins (total IgG, 
IgG subclasses) 
X
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X
X
X
X
Xv
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X
X
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X
X
X
W13 only
X
X
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X
X 
W13 only 
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X
X
X
X
X
X
X
X
X
X
X
X
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X
X
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 47 of 220
Screening 
Period
Do
se
Treatment Period
SFU Period
Visit(s)
1
BL
/2
3
4
5
6
7
8, 10, 
12,14, 16, 
18, 20, 22, 
24
9, 13, 17, 
21, 25
11, 15, 19, 
23
26
27
28
29
EW
EOS
b, c
Week
-4 to -1
1
1
2
3
4
5
6, 8, 10, 
12, 14, 
16, 18, 
20, 22
7, 11, 15, 
19, 23
9, 13, 17, 
21
24
25
28
32
Day
-28 to -1
1
3
8
15
22
29
36, 50, 
64, 78, 
92, 106, 
120, 134, 
148
43, 71, 
99, 127, 
155
57, 85, 
113, 141
162
169
190
218
Assessmentsa
Visit
Windowc
+2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
±2dd
Headache questionnairex
X
X
ADA= antidrug antibodies; AE=adverse event; AESM=adverse event of special monitoring; BP=blood pressure; BL=Baseline; d=day(s); COVID-
19=coronavirus disease 19; D=Day; DNA=deoxyribonucleic acid; ECG=electrocardiogram; EOS=End of Study; EQ-5D-5L=European Quality of Life Health 
Status Questionnaire-5 Dimensions, 5 Levels; EW=Early Withdrawal; GI=gastrointestinal; HIV=human immunodeficiency virus; ICF=Informed Consent 
Form; Ig=immunoglobulin; IMP=investigational medicinal product; IRT=interactive response technology; ITP=immune thrombocytopenia; ITP-PAQ=ITP 
Patient Assessment Questionnaire; PGI-C=Patient Global Impression of Change; PGI-S=Patient Global Impression of Severity; PK=pharmacokinetic; 
PRO=patient-reported outcomes; RNA=ribonucleic acid; SF-36: Short-Form 36-Item Health Survey; SFU=Safety Follow-Up; TB=tuberculosis; W=Week.
Site visit
Optional home visit (Home IMP administration and assessments are optional and can be conducted (if approved by regulatory agencies) at the sites as 
deemed necessary by site personnel and/or the study participant).
a The allowed time window for assessments is ±5 mins for assessments <30 mins and ±15 mins for assessments >30 mins.
b The EOS Visit is 8 weeks following the final dose.
c Study participants can withdraw at any time during the study, based on criteria in Section 7.
d The visit windows are relative to the Dosing Visit 1 date. At Day 3 a visit window of +2 days is allowed. For all remaining visits a visit window of +/-2 days is 
allowed. However there should be a minimum interval of 5 days and a maximum interval of 9 days between two doses of IMP. 
e The TP0004 ICF will be given to the study participants that are willing to enroll into TP0004.
f Will be used to check study participant’s eligibility for TP0004.
g If required, by site’s local procedure, the platelet count assessed by the local laboratory can be done -1 day for Baseline (Visit 2) and for W2 (Visit 4). For 
subsequent dosing visits, the last available platelet count can be considered.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 48 of 220
h Platelet counts can be taken at home visits; home visits are allowed if the previous 4 platelet counts were stable between 50 to 150×109/L and there was no dose 
change. If criteria are met, the visit may be conducted at home, administering the same dose of IMP as at the previous visit.
i Vital signs will include BP, pulse rate, and body temperature. On dosing days, for the first 2 weeks (W1, W2), vital signs will be measured prior to IMP 
administration, at the end of the infusion, and 4 hours after the end of the infusion. For the next 3 visits (W3, W4 and W5), vital signs will be measured prior to 
IMP administration, at the end of the infusion, and 1 hour after the end of the infusion. From W6, vital signs will be measured prior to IMP administration, at 
the end of the infusion, and 15 minutes after the end of infusion. At nondosing visits, vital signs need only be taken once during the visit. In case of dose 
increase, vital signs will be measured prior to IMP administration, at the end of infusion, and 1 hour after the end of infusion for the next 2 infusions. In case of 
untoward event, additional vital signs (unscheduled assessment) should be taken at the discretion of the investigator and post-observation time can be extended. 
These recommendations are applicable for dosing at site and at home.
j The ECG should be performed prior to blood collection for assessment of laboratory parameters (central reading of ECGs). ECGs have to be recorded at W1, 
Day 1 (predose and 4 hours postdose), W3 (predose), and W25.
k Vaccination titers against S. pneumoniae, N. meningitidis and H. influenzae (only in splenectomized participants) collected at W1 (Baseline), W3 (predose), 
EW Visit and EOS Visit.
l Vaccination titers against tetanus to be collected in all participants at Baseline (predose), W3 (predose), EW Visit, and EOS Visit
m For study participants who received COVID-19 vaccine prior to entry into TP0003, biomarker samples should be taken at Baseline (predose), EW Visit, and 
EOS Visit.
n For study participants who received COVID-19 vaccine during enrollment in TP0003, the collection of COVID-19 biomarkers baseline samples should occur 
predose, 2 to 3 weeks after the participant has received his/her last COVID vaccination (ie, second dose of a 2-dose vaccine, or booster). A second sample 
should be collected 3 months after last vaccination. There should be a minimum window of 72 hours between COVID vaccination and IMP administration.
o TB signs and symptoms questionnaire has to be completed at Screening, W1, W13, W25, and EOS Visit.
p On dosing days, for the first 2 weeks, a 4-hour post-dose observation will be in place. Assuming the first 2 doses were well tolerated, on dosing days at Week 
3, 4, and 5, a 1-hour post dose observation will be in place. Assuming the first 5 doses were well tolerated, on subsequent weeks, a 15-minute post-dose 
observation will be in place. However, if the dose needs to be decreased due to a TEAE(s) or dose needs to be increased, post dose observation will be extended 
to 1 hour after the end of infusion for the next 2 infusions. The post-dose observation time frame may be extended at the discretion of the investigator. These 
recommendations are applicable for dosing at site and at home. Approval from the investigator and sponsor is required prior to the start of home dosing.
q PK and ADA blood samples are to be taken predose unless otherwise indicated.
r PK and ADA samples to be taken predose and one additional sample within 1 to 5 days postdose following administration at W13 (Days 86 to 89) for PK and 
ADA and one additional sample within 1 to 5 days postdose at W24 (Days 163 to 166) for PK. 
s Serum complements (C3, C4) and plasma complements (C3a, C5a), should be taken predose at Baseline (Day 1) and W25 for all study participants. Additional 
samples should be collected 2 hours and 4 hours postevent or as soon as possible before the next IMP for study participants with infusion reaction or 
hypersensitivity reaction (see Section 8.3.8).
t Optional blood collection if study participant selects “yes” on the pharmacogenomics substudy ICF.
u Exploratory biomarker samples should be taken predose at Baseline (Day 1) and W25 for all study participants (see Section 8.9). Additional samples should be 
collected 4 hours postevent or as soon as possible before the next IMP for study participants with severe and/or serious headaches or severe and/or severe GI 
disorders (ie, abdominal pain, diarrhea, vomiting; see Section 8.3.8).
v If total IgG levels are <1g/L, ad hoc assessments (eg, additional IgG samples) may be performed to monitor recovery of IgG levels. Section 10.25.
w PROs to be completed prior to dosing and prior to any other study procedures.
x This assessment is applicable only to study participants experiencing moderate, severe and/or serious headaches and will be performed daily until resolution (ie, 
if headache becomes mild, normal collection of AEs should apply). This assessment can also be done remotely eg, via phone interview. 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 49 of 220
2
INTRODUCTION
Rozanolixizumab (UCB7665) is a humanized IgG 4P monoclonal antibody that is being 
developed as an inhibitor of the activity of the FcRn for IgG.
By blocking the activity of FcRn, rozanolixizumab accelerates the catabolism of IgG antibodies, 
including IgG autoantibodies. The aim is to reduce the concentration of pathogenic IgG in 
patients with autoimmune diseases mediated by the action of IgG autoantibodies.
The FcRn recycles IgG and albumin and transports it bidirectionally across epithelial barriers. 
Recent studies have shown that FcRn rescues both IgG and albumin from intracellular lysosomal 
degradation by recycling it from the sorting endosome to the cell surface (Roopenian and 
Akilesh, 2007). Neonatal Fc receptor may also mediate transcytosis of IgG to facilitate its 
distribution within tissues. Rozanolixizumab has been specifically designed to block IgG binding 
to FcRn without blocking the binding and recycling of albumin.
Rozanolixizumab binds with high affinity to FcRn at both neutral and acidic pH. 
Immunoglobulin G that is constitutively taken up by pinocytosis into cells fails to bind to FcRn, 
even at the acidic pH found in the endosome. It is therefore not recycled and is trafficked to the 
lysosomes for degradation.
Production of pathogenic IgG autoantibodies is the major pathophysiology leading to a number 
of autoimmune diseases, which include ITP, myasthenia gravis (MG), pemphigus vulgaris, 
Goodpasture’s syndrome, neuromyelitis optica, Guillain-Barré Syndrome, and chronic 
inflammatory demyelinating polyradiculoneuropathy (CIDP).
As individual disease entities, IgG autoantibody-mediated conditions are relatively rare. 
Treatment of these disorders remains a difficult clinical problem, requiring in many of these 
conditions the long-term use of corticosteroids alone or combined with other immunomodulatory 
agents. These therapeutic approaches are not effective in all patients and conditions and have 
broad immunosuppressive effects causing considerable toxicity and treatment-related morbidity.
Treatments aimed at reducing the quantity of circulating IgG autoantibodies, including 
plasmapheresis, immunoadsorption, or high dose IVIg, are being used for primary and secondary
therapy of autoimmune diseases. The therapeutic approach of these treatments is thought in part 
to be based on lowering levels of pathogenic autoantibodies, which represents rational and 
effective treatment modalities of autoimmune diseases.
Therefore, specific and sustained removal of the IgG autoantibodies by FcRn blockade may 
provide an effective therapeutic option for IgG autoantibody-mediated autoimmune disorders.
More detailed information regarding the nonclinical and clinical development programs for 
rozanolixizumab, including all completed and ongoing studies, can be found in the Investigator’s 
Brochure (IB).
2.1
Study rationale
Immune thrombocytopenia, previously defined as immune thrombocytopenic purpura and 
idiopathic thrombocytopenic purpura (Rodeghiero et al, 2009), is a rare, orphan hematological 
autoimmune disease characterized by an isolated low platelet count (thrombocytopenia) caused 
by specific antibodies directed against platelets and the absence of other causes of 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 50 of 220
thrombocytopenia. In a pathological disease state these platelets are coated with autoantibodies 
to platelet membrane antigens, resulting in splenic sequestration and phagocytosis by 
mononuclear macrophages. The resulting shortened life span of platelets in the circulation, 
together with platelet underproduction by autoantibody-mediated megakaryocytes inhibition 
results in a decreased platelet count (Arnold et al, 2015; McMillan et al, 2004).
The spleen is the key organ in the pathophysiology of ITP, as it is the site of autoantibody
production (white pulp) and the site of phagocytosis of autoantibody-coated platelets (red pulp). 
The slow passage of platelets through splenic sinusoids with a high local concentration of 
antibodies, and Fc-gamma receptors on splenic macrophages supports the role of the spleen as a 
site of platelet destruction (Sandler, 2000).
Recently, new definitions for the phases of the disease were introduced (Rodeghiero et al, 2009). 
Based on the time from diagnosis, the first phase (up to 3 months) is the “newly-diagnosed ITP 
phase;” phase 2 (>3 months up to 12 months) is the “persistent phase;” and after 12 months, the 
“chronic phase” starts. These phases also reflect the line of treatment.
The major goal for treatment of ITP is to achieve a platelet count that prevents major bleeding, 
rather than correcting the platelet count to normal levels. The management of ITP should be 
tailored to the individual patient and it is rarely indicated in those with platelet counts >50×109/L 
in the absence of bleeding, trauma, surgery, or high-risk factors (eg, patients on anticoagulation 
therapy) (EMA/CHMP/153191/2013, 2014). However, there is general agreement that adults 
with a count of <30×109/L with bleeding at diagnosis require treatment.
The first line of treatment for newly-diagnosed ITP is generally agreed and is based on the use of 
corticosteroids and IVIg. Although corticosteroids are effective, their long-term use is not 
recommended due to concerns over their safety (eg, osteoporosis, hypertension, 
immunosuppression). Patients who fail to respond or who relapse face the options of treatment 
with second line drug therapy or splenectomy, but there is no clear evidence to support the best 
approach (Rodeghiero et al, 2009; Provan et al, 2010; Neunert, 2011). Splenectomy can provide 
long-term efficacy in approximately 60% of cases, and recent guidelines suggest considering a 
splenectomy after 12 months. Splenectomy is an invasive procedure associated with acute 
complications (due to thrombocytopenia-like bleeding events) and long-term complications from 
loss of splenic functions. Asplenic individuals are at an increased risk of life-threatening 
infections, although minimized with vaccination prophylaxis. Splenectomy may increase 
morbidity from venous thromboembolism or atherosclerosis (Ghanima et al, 2012). Second-line 
drug therapies include high dose dexamethasone or methylprednisolone; high dose IVIg or 
anti-D Ig; vinca alkaloids; dapsone and danazol; the immunosuppressants cyclophosphamide, 
azathioprine, and cyclosporine; or mycophenolate mofetil and Helicobacter pylori eradication if 
applicable. The anti-CD20 monoclonal antibody rituximab, even if not licensed for the treatment 
of ITP, and the thrombopoietin-receptor agonists (eltrombopag, romiplostim [both approved in 
the US and Europe] and avatrombopag [approved in the US in 2019]) are considered as second 
line (Ghanima et al, 2018) as well as third line options. In 2018, in the US, fostamatinib, a 
SYK-inhibitor, has been approved for the treatment of chronic ITP. Each of these treatments 
discussed above has unique benefits, limitations, tolerability considerations, and risks. Taking 
the side-effect profile and long-term complications of existing treatments together, there remains 
a considerable unmet medical need for novel therapeutic options in the treatment of persistent 
and chronic ITP.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 51 of 220
By blocking the activity of FcRn, rozanolixizumab accelerates the catabolism of antibodies and 
reduces the concentration of pathogenic IgG in primary ITP patients, thus potentially offering a 
safe, effective, and convenient alternative to existing treatments. This Phase 3 study will provide 
the required data to establish the safety and efficacy of rozanolixizumab in study participants 
with persistent or chronic primary ITP who have failed or were intolerant to two or more prior 
therapy and who require an increase and sustained effect in their platelet counts.
2.2
Background
To date, rozanolixizumab has been administered to human study participants in 9 clinical studies: 
UP0018, UP0060, CIDP01, CIDP04, MG0002, MG0003, MG0004, and its replacement study 
MG0007, and TP0001. UP0018 is a completed first-in-human (FIH) study. MG0002 is a 
completed Phase 2a study in participants with generalized MG, TP0001 is a completed Phase 2 
study in study participants with primary ITP, and CIDP01 is a completed Phase 2a study in study 
participants with CIDP. UP0060 is a Phase 1 study in healthy volunteers, CIPD04 (OLE) is an 
ongoing Phase 2a study in study participants with CIDP, and MG0003 and MG0004 (OLE 
replaced by MG0007) are ongoing Phase 3 studies in study participants with generalized MG.
UP0018 was conducted in 49 healthy study participants. The study evaluated the safety, 
tolerability, pharmacokinetic (PK), and PD effect on total IgG levels of single ascending doses of 
intravenous (iv) and sc rozanolixizumab. Doses of rozanolixizumab 
 were administered by both iv and sc routes in 3 cohorts, respectively, as 
There were no deaths or SAEs reported during UP0018, and no study participants discontinued 
the study due to TEAEs. Rozanolixizumab was tolerated with an acceptable safety profile after 
the single administration of 
 and 
 (both iv and sc) and 
 sc doses. 
Four TEAEs with a maximum intensity of severe were reported in this study: headache 
(3 participants [50.0%]) and back pain (1 participant [16.7%]); all of which were reported in the 
rozanolixizumab 
 iv group. For sc administration of rozanolixizumab, the most frequently 
reported TEAEs were headache (5 participants [27.8%]), and back pain and diarrhea (each 
reported by 3 participants [16.7%]). No severe adverse events (AEs) were reported following sc 
administration. The peak and total exposure of rozanolixizumab showed nonlinear increases 
consistent with target-mediated drug disposition. Dose-dependent statistically significant 
reductions in levels of total IgG and dose-dependent reductions in levels of IgG subclasses 
(IgG 1 to 4) were observed after rozanolixizumab was administered by iv or sc routes.
UP0060 is a randomized, participant-blind, investigator-blind, placebo-controlled, single dose-
ascending, cohort design to compare the safety, tolerability, and PK of rozanolixizumab, and to 
explore the PD of rozanolixizumab administered by sc infusion in Japanese, Chinese, and 
Caucasian healthy study participants.
CIDP01 is a completed Phase 2a, multicenter, randomized, participant-blind, investigator-blind, 
placebo-controlled, parallel-group study with the primary objective of evaluating the clinical 
efficacy of rozanolixizumab as a treatment for study participants with CIDP. There were 
2 treatment arms in this study: 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 52 of 220
Overall, 
administration of rozanolixizumab at a dose level of 
sc was generally 
 and well tolerated, with an acceptable safety profile. No new safety concerns were 
identified. The incidence of TEAEs was similar between the rozanolixizumab and placebo 
groups, with the exception of the TEAE of injection/infusion site reactions which was reported at 
a higher frequency in study participants treated with rozanolixizumab. The majority of TEAEs 
were of mild to moderate intensity. The only severe TEAEs reported were in the context of 
underlying CIDP. During the Treatment Period, 10 (58.8%) study participants in the 
rozanolixizumab group and 5 (29.4%) in the placebo group experienced at least 1 drug-related 
TEAE. During the Observation Period, 1 (5.9%) study participant each in the rozanolixizumab 
and placebo groups experienced at least 1 drug-related TEAE. Two (11.8%) study participants in 
the rozanolixizumab group experienced serious TEAEs of CIDP relapse which were in the 
context of their underlying CIDP. No cases of severe headache, moderate or severe abdominal 
pain, moderate or severe vomiting, or severe diarrhea were reported. One (5.9%) study 
participant each in the rozanolixizumab and placebo groups experienced moderate diarrhea. No 
clinically meaningful trends were observed for clinical laboratory evaluations, vital signs 
measurements, or physical examinations. 
CIDP04 is an ongoing Phase 2a, multicenter, open-label extension study to investigate the long-
term safety, tolerability, and efficacy of rozanolixizumab in participants with CIDP. The study 
includes 
.
MG0002 is a completed Phase 2a, multicenter, randomized, investigator- and participant-blind, 
placebo-controlled, treatment sequence study evaluating the safety, tolerability, and efficacy of 
rozanolixizumab in study participants with generalized MG. The study included 2 Dosing 
Periods with  doses of IMP at 
 intervals each:
The primary efficacy variable was the change from Baseline in Quantitative MG score (a 
measure of muscular strength) to Day 29.
Overall, repeated administrations of rozanolixizumab at dose levels of 
 sc 
were generally considered 
and well tolerated, with an acceptable safety profile. No new 
safety concerns were identified in MG0002. The TEAE profile was similar between 
rozanolixizumab and placebo except for headaches where increased frequency and severity was 
observed in the rozanolixizumab-treated patients.
MG0003 is an ongoing Phase 3 multicenter, randomized, double-blind, placebo-controlled, 
3-arm, repeat-dose study evaluating the efficacy and safety of 2 doses (equivalent to 
 and 
) of rozanolixizumab and matching placebo 
administered 
 over a period of 6 weeks 
 in study participants with 
generalized MG who experience moderate to severe symptoms and are being considered for 
treatment with IVIg or plasma exchange (PEX).
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 53 of 220
TP0001 is a completed, Phase 2, multicenter, open-label, multiple-arm study to evaluate the 
safety and tolerability of rozanolixizumab in study participants with primary persistent and 
chronic ITP. The following dose arms were used in the study:
•
Dose Arm 1 (15 participants): rozanolixizumab 4mg/kg sc (5 doses at 1-week intervals)
•
Dose Arm 2 (15 participants): rozanolixizumab 7mg/kg sc (3 doses at 1-week intervals)
•
Dose Arm 3 (12 participants): rozanolixizumab 10mg/kg sc (2 doses at 1-week intervals)
•
Dose Arm 4 (12 participants): rozanolixizumab 15mg/kg sc (1 dose)
•
Dose Arm 5 (12 participants): rozanolixizumab 20mg/kg sc (1 dose)
Data from study TP0001 indicate that rozanolixizumab was tolerated with an acceptable safety 
profile after multiple (4mg/kg, 7mg/kg, and 10mg/kg) and single (15mg/kg and 20mg/kg) doses. 
The most frequent AE was headache (mild to moderate in intensity) and no severe headache was 
reported. There were no TEAEs leading to IMP discontinuation. Four serious TEAEs were 
reported overall (none were considered to be treatment-related by the investigator and were 
related to the underlying disease). A dose-dependent decrease in total IgG was observed: 43.6% 
(range 21.9% to 68.6%) for the 4mg/kg group (~Day 29), 49.9% (range 29.5% to 65.5%) for the 
7mg/kg group (~Day 22), 63.8% (range 38.4% to 75.0%) for the 10mg/kg group (~Day 15), and 
on Day 8, after a single dose, for the 15mg/kg and 20mg/kg groups 52.3% (range 30.1% to 
68.0%) and 60.2% (range 51.8% to 65.4%), respectively. Responders were classified as having a 
clinically relevant platelet response (≥50×109/L). Five (35.7%) participants in the 4mg/kg and 
7mg/kg groups, 5 (45.5%) of 11 participants in the 10mg/kg group, 8 (66.7%) of 12 participants 
in the single administration 15mg/kg dose group, and 6 (54.5%) of 12 participants in the single 
administration 20mg/kg group were clinically relevant responders.
Based on the above, UCB considers that TP0001 established supportive evidence of efficacy and 
safety and is proceeding with the development of rozanolixizumab for the treatment of adults 
with persistent or chronic primary ITP. UCB is proposing a clinical development Phase 3 
program in this orphan disease population comprised of two placebo-controlled, confirmatory 
maintenance treatment efficacy and safety studies, TP0003 and TP0006, and a one-year 
long-term safety, OLE study, TP0004.
The current study, TP0003, will assess the efficacy, safety, and tolerability of rozanolixizumab 
administered as a fixed-unit dose equivalent to 
 QW via sc infusion in adult study 
participants with persistent or chronic primary ITP.
2.3
Benefit/risk assessment
Although there were a number of treatment options approved for chronic ITP in the recent years, 
there is still an unmet medical need as for many of these medications the effect diminishes over 
time. The current available therapies like thrombopoietin-receptor agonists (TPO-RAs) have 
dietary exclusions, require liver function test monitoring or are increasing the risk of thrombosis 
or thromboembolic events. Corticosteroids are associated with significant long-term side effects. 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 54 of 220
Thus, there is an unmet medical need for new treatments that can reduce the complexity of the 
existing therapies.
The clinical efficacy data obtained in the Phase 2 study TP0001 indicate that rozanolixizumab 
has a rapid effect on lowering IgG and rapid onset of response in platelet count (increase in 
platelet count >50×109/L ) and an acceptable safety profile. The ability to administer via sc 
infusion results in low systemic fluid volumes with no impact on plasma viscosity, significant 
reduction in time for infusion, and reduced potential for infusion reactions. 
The clinical safety data to date indicate that rozanolixizumab is well tolerated, and the common 
side effects are generally mild to moderate in severity, can be monitored and are manageable.
The most common adverse drug reactions observed after use of rozanolixizumab across 
indications are headaches and gastrointestinal (GI) disturbances (diarrhea, nausea, vomiting). 
Potential risks are serious infusion/hypersensitivity reactions, serious infections, and effects on 
vaccination response. 
The risks of serious infusion/hypersensitivity and serious infections can be mitigated by careful 
monitoring, exclusion of at-risk study participants, and appropriate protocol withdrawal and 
stopping criteria. Additionally, protocol guidance for management of GI disturbances, severe 
and/or serious headaches, and infusions is also provided as well as expedited reporting 
requirements of AESM. 
Restrictions on use of live vaccines have been defined in the Exclusion Criterion #21a. If 
vaccination with non-live vaccines (including COVID-19 vaccines) is considered necessary once 
a study participant has started therapy with IMP, the degree of protection afforded with a vaccine 
may be compromised while the participant is being treated with IMP.
Based on its mechanism of action, rozanolixizumab will reduce total IgG levels including 
vaccine specific IgG. However, it is unlikely that the immunogenicity of vaccine will be 
compromised by FcRn inhibition.  Given the study population characteristics (eg, status of the 
underlying disease, concomitant immunosuppressive therapies, etc.,) it is recommended to 
perform individualized benefit risk assessment for vaccination and specifically vaccination 
against COVID-19 infection. If vaccination is planned, information regarding vaccine should be 
recorded (Section 6.4.1). Vaccination should be scheduled, if at all possible, to allow 
differentiation of safety profiles of IMP and vaccine (eg, a minimum window of 72 hours 
between COVID-19 vaccination and IMP administration). If any AEs were to occur, they should 
be handled as described in (Section 8.3.10) with causality assessment provided for both IMP and 
vaccine. Additionally, to further characterize the effect of rozanolixizumab on vaccination 
response, measurement of vaccine titers are being tested in our development programs.  
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of rozanolixizumab may be found in the current version of the IB.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 55 of 220
3
OBJECTIVES AND ENDPOINTS
The objectives and corresponding endpoints for this study are presented in Table 3-1.
Table 3-1:
Study objectives and endpoints
Objectives
Endpoints
Primary
•
To demonstrate the clinical efficacy of 
rozanolixizumab in maintenance 
treatment in study participants with 
primary ITP
The primary efficacy endpoint is:
•
Durable Clinically Meaningful Platelet 
Response of ≥50×109/L, for at least 8 out of 
12 weeks during the last 12 weeks (Week 
13 to 25)
The secondary efficacy endpoints are:
•
Cumulative number of weeks with 
Clinically Meaningful Platelet Response of 
≥50×109/L over the 24-week treatment 
period
•
Time to first Clinically Meaningful Platelet 
Response of ≥50×109/L: time from starting 
treatment to achievement of first response 
of ≥50×109/L 
•
Clinically Meaningful Platelet Response of 
≥50×109/L by Day 8
•
Response defined as platelet count 
≥30×109/L and at least a 2-fold increase of 
the Baseline count confirmed on at least 
2 separate occasions at two adjacent 
nominal visits at least 7 days apart, and 
absence of bleeding by visit a,b
•
Time to first rescue therapy
•
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 56 of 220
The other efficacy endpoints are:
•
Duration of first Clinically Meaningful 
Platelet Response of ≥50×109/L: measured 
from achievement of first Response to loss 
of first Response (loss of Response defined 
as platelet count <50×109/L)
•
Time to first Response: time from starting 
treatment to achievement of Response 
•
Usage of rescue therapy by visit
•
Complete Response defined as platelet 
count ≥100×109/L confirmed on at least 
2 separate occasions at two adjacent 
nominal visits at least 7 days apart, and 
absence of bleeding by visit a,b
•
Cumulative number of weeks over the 
planned 24-week treatment period with 
platelet counts of ≥100×109/L
•
Cumulative number of weeks over the 
planned 24-week treatment period with 
platelet counts ≥30×109/L and at least 
doubling from Baseline
•
Mean change from Baseline in platelet 
count by visit
•
Clinically Meaningful Platelet Response of 
≥50×109/L, for at least 4 out of 6 weeks 
during the last 6 weeks (Week 19 to 25).
•
Clinically Meaningful Platelet Response of 
≥50×109/L, for at least 6 out of 8 weeks 
during the last 8 weeks (Week 17 to 25).
Secondary
•
To assess the safety and tolerability of 
rozanolixizumab 
The safety endpoints are:
•
Occurrence of TEAEs
•
Occurrence of TEAEs leading to 
withdrawal of IMP (ie, study 
discontinuation)
The other safety endpoints are:
•
Occurrence of serious TEAEs
•
Occurrence of treatment related TEAEs
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 57 of 220
•
Occurrence of AESM
•
Vital signs change from Baseline (BP, 
pulse rate, body temperature) at each 
scheduled assessment during Treatment and 
SFU Periods
•
12-lead ECG change from Baseline at each 
scheduled ECG visit 
•
Laboratory change from Baseline 
(hematology including coagulation 
parameters, clinical chemistry, and 
urinalysis) at each scheduled assessment 
during Treatment and SFU Periods
•
Change from Baseline in concentrations of 
total protein and albumin 
•
Change from Baseline in serum 
complement levels (C3 and C4) and plasma 
complement levels (C3a and C5a) at each 
scheduled assessment during the study (for 
study participants experiencing infusion 
reactions or hypersensitivity reactions)
Exploratory
•
To evaluate the clinical efficacy as 
measured by the ITP bleeding score
•
ITP-BAT bleeding events and severity by 
visit
•
To assess the effect of rozanolixizumab 
on health-related quality of life 
(HRQoL)
•
Change from Baseline in European Quality 
of Life (EuroQol) -5 dimension 5 Levels 
(EQ-5D-5L) item responses
•
Change from Baseline in Short form 
36-item (SF-36) domain and composite 
scores
•
Change from Baseline in the ITP-PAQ 
domain scores
•
To assess hospitalizations due to ITP
•
Number and length of hospitalizations
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 58 of 220
•
To assess the effect of rozanolixizumab 
on patient reported outcomes (PROs)
•
Change from Baseline in FATIGUE-PRO 
Physical Fatigue Score
•
Change from Baseline in Patient Global 
Impression of Severity (PGI-S)
•
Patient Global Impression of Change 
(PGI-C) at all available post-baseline 
assessments
•
To assess the pharmacokinetics of 
rozanolixizumab administered by 
subcutaneous (sc) infusion
•
Plasma concentration of rozanolixizumab 
•
To evaluate the incidence and emergence 
of antidrug antibodies (ADAs) of 
rozanolixizumab
•
ADAs at each scheduled assessment 
•
To assess the pharmacodynamic (PD) 
effects of rozanolixizumab
The exploratory PD endpoints are:
•
Total serum IgG (absolute value) and 
change from Baseline (absolute values and 
percentage) in serum IgG and in serum IgG 
subclass concentration at each scheduled 
assessment
•
Absolute values and change from Baseline 
(absolute values and percentage) in serum 
immunoglobulin concentrations (IgA, IgE, 
IgM) at each scheduled assessment
•
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rozanolixizumab treatment on 
vaccination titers
•
Percent change from Baseline in 
vaccination titers against Streptococcus 
pneumoniae, Neisseria meningitidis, and 
Haemophilus influenzae in splenectomized 
study participants
•
Percent change from Baseline in 
vaccination titers against tetanus in all 
study participants
•
To assess the effect of rozanolixizumab 
on response to vaccination in study 
participants who received COVID-19
vaccine
•
Change in biomarkers of COVID-19 
vaccine response over time
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 59 of 220
4
STUDY DESIGN
4.1
Overall design
This is a Phase 3, multicenter, double-blind, randomized, placebo-controlled study with 
rozanolixizumab in study participants with persistent or chronic primary ITP defined as more 
than 3 months, or 12 months of duration, respectively, since diagnosis.
The study participants will be male and female adults with persistent or chronic primary ITP, a 
platelet count measurement at Screening and at Baseline with an average of the two <30×109/L 
(no single count may be >35×109/L) and a documented history of low platelet count prior to 
Screening.
The primary objective of TP0003 is to evaluate the clinical efficacy of rozanolixizumab as a 
maintenance treatment in participants with persistent or chronic primary ITP. 
The study design was selected to assess whether multiple sc infusions of rozanolixizumab will 
result in a durable Clinically Meaningful Platelet count increase of ≥50×109/L, for at least 8 out 
of 12 weeks during the last 12 weeks of the Treatment Period (Week 13 to 25). On Day 1 
(Baseline Visit), study participants will be randomized 2:1 to receive a fixed-unit dose of 
rozanolixizumab equivalent to 
or placebo QW until Week 24, with randomization 
stratified by the degree of thrombocytopenia (platelet count < or ≥15×109/L) and history of 
splenectomy (yes or no). The last assessments prior to the SFU Visit will be done at Week 25. 
Study participants will be observed during the 8-week SFU Period after the final administered 
dose. The TP0003 study schematic is presented in Figure 1-2.
The total maximum study duration per study participant is up to 35 weeks, including a Screening 
Period (up to 4 weeks), a Dose Adaptation Period (12 weeks), a Maintenance Period (12 weeks) 
and an SFU Period (8 weeks after final dose administered). Splenectomized participants will be 
required to attend a Prolonged Screening Period prior to the Screening Visit in order to receive, 
if applicable, the required vaccinations, which will extend the total study duration by up to 20 
weeks.
The eligibility of study participants to participate in the study will be determined during the 
Screening Period. Once eligibility is confirmed, the study participants will come to the site on 
Day 1 (Baseline Visit) and receive a single fixed-unit dose of rozanolixizumab or placebo 
administered sc (based on randomization).
Rozanolixizumab or placebo will be administered as a sc infusion with an infusion pump at a 
. A fixed-unit dose across different body weight tiers, as 
presented in Table 1-2 will be applied. 
If the participant is unable to tolerate a 
, 
 may be used at the discretion 
of the clinical personnel administering the infusion. 
The placebo arm will use 0.9% sodium chloride aqueous solution (physiological saline, 
preservative-free) for sc administration, matching the volumes of the rozanolixizumab arm.
Dosing will be followed by a series of postdose study assessments on Day 1 through Day 169, 
with a subsequent SFU Period through Day 218. On dosing days, for the first 2 weeks, a 4-hour 
post-dose observation will be in place. Assuming the first 2 doses were well tolerated, on dosing 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 60 of 220
days in Week 3, 4, and 5, a 1-hour post dose observation will be in place. Assuming the first 5 
doses were well tolerated, on subsequent weeks, a 15-minute post-dose observation will be in 
place. However, if the dose needs to be decreased due to a TEAE(s) or dose needs to be 
increased, post dose observation will be extended to 1 hour after the end of infusion for the next 
2 infusions. The post-dose observation time frame may be extended at the discretion of the 
investigator. These recommendations are applicable for dosing at site and at home. Approval 
from the investigator and sponsor is required prior to the start of home dosing. 
In exceptional circumstances (eg, pandemic, hurricanes, etc) where study-specific investigations 
may not be conducted according to study protocol, contingency measures will be in place (see 
Section 8).
Approximately 150 study participants will be screened at approximately 70 sites from North 
America, Europe and Asia to achieve the targeted number of approximately 60 study participants 
randomized to weekly dosing.
All study participants completing the Treatment Period (with or without the need for rescue 
therapy) and fulfilling the OLE study (TP0004) eligibility criteria will be allowed to enroll into 
TP0004.
If study participants require rescue therapy during the Treatment Period (Week 1 to Week 25), 
they are allowed to receive commercially available rescue therapy (Section 6.4.3).
An external IDMC will be established to review the safety data at predefined intervals and ad 
hoc as needed, should emerging safety concerns arise during the study. The first IDMC meeting 
for the review of safety data is planned to occur after approximately 15 participants have
received 3 doses of IMP in TP0003. The study will be put on hold if any of the following occurs:
•
The IDMC judges it necessary for medical or safety reasons and
•
The sponsor or its designee judges it necessary for medical, safety, regulatory, or any other 
reasons consistent with applicable laws, regulations and Good Clinical Practice.
•
Three study participants experience any SAE of same type within the first 15 study 
participants who have received 3 doses of IMP across TP0003 and TP0006, unless the SAE 
is clearly unrelated to the study drug. After protocol amendment 3, this rule no longer 
applies. 
−
For US and Canada only: Three study participants experience any SAE within the first 
15 study participants who have received at least one dose of IMP across TP0003 and 
TP0006, unless the SAE is clearly unrelated to the study drug.
The IDMC has the possibility to unblind the data. Details of the IDMC composition, processes, 
and responsibilities will be documented in the IDMC charter. It is intended to have one IDMC 
for both of the pivotal studies (TP0003 and TP0006), where the data will be presented unpooled, 
ie, data from each study will be reviewed separately. Key safety data may be pooled at the 
discretion of the IDMC for protection of all study participants if warranted. 
Based on feedback from the IDMC, weekly dosing was implemented in protocol amendment 3. 
Study participants being treated with the bi-weekly dosing regimen will switch to the weekly 
dosing regimen once protocol amendment 3 is approved at the respective study site. 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 61 of 220
Additionally, a Safety Signal Detection Team will perform rozanolixizumab program-wide 
aggregated safety data reviews at predefined intervals.
4.2
Scientific rationale for study design
Autoantibodies against platelet antigens are considered to be a hallmark of ITP. Production of 
pathogenic IgG autoantibodies by plasma cells is accepted as the central underlying 
pathophysiological mechanism in a number of IgG-mediated autoimmune diseases, which 
include ITP.
Treatments aimed at reducing the quantity of circulating IgG autoantibodies are being used for 
primary and secondary therapy of autoimmune diseases, particularly where corticosteroid-based 
immune suppression is not or no longer effective. The therapeutic approach of these treatments is 
based on lowering levels of pathogenic autoantibodies, which represents rational and effective 
treatment modalities of autoimmune diseases.
TP0003 is designed to evaluate the efficacy, safety, and tolerability of rozanolixizumab given as 
fixed-unit doses equivalent to 
, weekly until Week 24 in adult study 
participants with primary ITP.
Historical clinical data have demonstrated that the likelihood of bleeding is reduced with platelet 
counts >50×109/L, including both spontaneous bleeding and bleeding during minor surgical 
interventions such as dental manipulations. Conversely, the likelihood of bleeding events 
increases with platelet counts <35×109/L, with bleeding risk increasing as platelet count 
decreases. Hence, the participant population to be enrolled into this study should have a 
diagnosis of primary ITP (persistent or chronic) and a platelet count of <30×109/L. Study 
participants with clear evidence of a secondary cause of ITP and study participants with chronic 
or latent infections or active infections are excluded.
Safety and tolerability of rozanolixizumab up to 
sc and iv doses have been evaluated in 
healthy study participants in study UP0018. In the subsequent Phase 2 study TP0001, in study 
participants with primary persistent and chronic ITP, different dosing regimens were tested, and 
a dose up to 15mg/kg as a single sc infusion was well tolerated and showed a 67% clinically 
meaningful responder rate, defined as platelet count increases to ≥50×109/L. In CIDP01, 34 
study participants randomized to IMP (1:1 placebo:rozanolixizumab) followed 
 doses 
of 
 administrations. Of the 34 study participants, 21 study participants rolled over into
the ongoing 52-week OLE study CIDP04. At least 6 participants have been treated with a 
 sc infusion for 1 year. Rozanolixizumab was well tolerated to date and the 
results of these two studies support the dosing regimen of 
 for 24 weeks 
in this study. 
A 24-week Treatment Period to initiate and maintain a platelet increase and a subsequent 8-week 
SFU Period is considered sufficiently long to evaluate a difference between rozanolixizumab 
treatment and placebo.
It is generally recognized that a double-blind, randomized, parallel, placebo-controlled study is 
the most robust means of assessing the efficacy of a new treatment. The EMA guideline on the 
clinical development of medicinal products intended for the treatment of chronic ITP (effective 
as of Sep 2014) proposes a double-blind, placebo-controlled design. The placebo arm is justified, 
as rescue therapy and background treatment for ITP is allowed, provided the medication has 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 62 of 220
been taken on a stable dose for a certain period of time and below a maximum dose as specified 
in Table 6-2.
4.3
Justification for dose
Initially, a fixed-unit dosing regimen across body weight tiers equivalent to 
(starting 
dose) followed by 
 (maintenance doses) every 2 weeks (Q2W) was proposed for use in 
the confirmatory TP0003 study, based upon response rate (>50×109/L), time to onset of the 
platelet count increase, and safety profile observed in the Phase 2 study, TP0001. Data from 
TP0001 showed that a single dose of 
 reached a 52% decrease in IgG from Baseline by 
Day 8, and a clinical response was observed for most study participants in the cohort before the 
IgG nadir on Day 8. The study also showed that the median (and range) duration of platelet 
response (platelet count >50×109/L) following a dose of 
 QW and a single dose of 
 was 12 (6 to 19) days and 11.96 (6 to 20) days, respectively. Hence, a starting dose of 
 followed by 
 Q2W was expected to sustain IgG levels 
reduced from its Baseline level by >50% and expected to be sufficient to translate into a relevant 
platelet response. Dose adjustments to 
 or approximately 
 were allowed if 
medically indicated, eg, for thrombocytosis. The proposed dose regimens were stratified by 
weight tiers as presented in Table 1-2.
Following the IDMC data review and the available OLE TP0004 data with the initially proposed 
dose regimen of 
, the IgG reductions appear to be in concordance with the anticipated 
reductions of ~50%, however the observed platelet count data are not sustained in TP0004 
during the 
 dosing interval. Protocol Amendment 3 follows the advice from the 
external IDMC to increase the frequency of dosing, as in the OLE study TP0004 platelets are not 
sustained over a 
 dosing interval (observed platelet levels <50×109/L). Following the 
advice, the dose regimen for study TP0003 and OLE TP0004 will be changed to 
 
QW. This dose regimen is anticipated to be 
 and more likely to sustain the 
platelets  across the dosing interval reducing the risks associated with low platelet counts. A dose 
of 
 QW is predicted to sustain IgG levels with mean percentage change from 
Baseline reduction of 70% and maintain FcRn receptor occupancy (RO%) levels above 50% 
throughout the dosing interval as opposed to the Q2W that only sustained it above this level 
during the first week following each dose and not for the entire 14-day period between doses. 
A 
 QW dose regimen is anticipated to achieve similar level of RO% to a 
, with a range on RO% from peak to trough of 99 to 50% during the 
7 days dosing interval. A minimal difference in IgG reduction between 
during the first 7 days was already observed in TP0001. Based on the minimal advantage from a 
RO% and IgG reduction perspective that a 
starting dose will provide, the starting dose 
of 
 is therefore no longer required with the 
 QW dose regimen. The 
 QW dose is predicted to achieve mean concentrations at steady state (Cmax,ss) 
of ~30ug/mL (2 days post dose) and Ctrough of 0.31ug/mL. 
In terms of safety, 
 weekly doses have been tested in TP0001 and showed a good 
safety and tolerability profile. In addition, this dose regimen of 
 QW has been studied in 
other indications like CIDP01, where 34 study participants (1:1 placebo:rozanolixizumab) 
followed 
 doses of 
 administrations. Of the 34 study participants, 21 study 
participants rolled over into the ongoing 52-week OLE study CIDP04. At least 6 participants 
have been treated with a
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 doses were
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 63 of 220
generally 
 and well tolerated, with an acceptable safety profile and no new safety concerns 
were identified. 
In addition, in order to avoid platelet count increases to ≥150×109/L, down-titration of the IMP 
dose level as described in Table 1-1 will be allowed. Weekly platelet assessments will be 
performed during the study, to support the dosing strategy with the aim to increase platelet 
counts ≥50×109/L and to minimize platelet counts ≥150×109/L in the study participants. Up 
titration to fixed-unit doses of 
rozanolixizumab 
 QW will also be allowed to 
maintain stable platelet counts of ≥50×109/L over the Treatment Period if a previous down 
titration has occurred and subsequently platelet counts dropped again to below 50×109/L.
In summary, the new proposed dose regimen for Phase 3 is a 
 QW dose as 
starting and maintenance dose, allowing to down-titrate to 
 total dose based 
on the efficacy and safety profile. This regimen is supported by the observed data in the program 
thus far.
4.4
End of study definition
A study participant is considered to have completed the study if he/she has completed all phases 
of the study including the SFU Period, or has successfully been enrolled into TP0004 at Week 25 
(Visit 27). Study participants not rolling over into TP0004 will have an EOS Visit performed 
8 weeks after the final dose of IMP, or upon discontinuation of the study.
The enrollment into the TP0004 study should be conducted on the same day as Visit 27 
(Week 25) of the feeder study. In case the enrollment into TP0004 is not conducted at 
Week 25 (Visit 27) a visit window of +3 days will be granted; therefore, rollover needs to be 
completed 3 days after Week 25 at the latest. 
The EOS is defined as the date of the last visit of the last participant in the study.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 64 of 220
5
STUDY POPULATION
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted.
5.1
Inclusion criteria
Study participants are eligible to be included in the study only if all of the following criteria 
apply:
Age
1a. Study participant must be ≥18 years of age at the time of the Screening Visit. For 
Japan-specific regulations, see Appendix 8, Section 10.8.
Type of participant and disease characteristics
2. Study participant is considered reliable and capable of adhering to the protocol, visit 
schedule, or medication intake according to the judgment of the investigator.
3. Study participant has a diagnosis of persistent (>3 months duration) or chronic (>12 months 
duration) primary ITP at the Screening Visit.
4b. Study participant has a documented intolerance or insufficient response to two or more 
appropriate standard of care ITP treatments (including but not limited to corticosteroids, 
immunoglobulins, TPO-RAs, azathioprine, danazol, cyclophosphamide, and/or rituximab or 
other immunosuppressants, splenectomy) prior to Screening. Two or more appropriate ITP 
treatments are defined as either at least two prior treatments if the participant is not taking 
concurrent ITP medications, or if the participant is on a concurrent ITP treatment at the study 
start (Screening), has received at least one prior ITP treatment.
5. Study participants must have prior history of a response to a previous ITP therapy. 
6a. If taking allowed drugs (see Table 6-2), study participant must be on stable doses during 
defined time periods prior to Baseline (Day 1).
7. Study participant has a documented history of low platelet count (<30×109/L) prior to 
Screening. 
8. Study participant has a platelet count measurement at Screening and at Baseline (Day 1) with 
an average of the two <30×109/L and no single count may be >35×109/L (using local 
laboratories).
9. Study participant has a current or history of a peripheral blood smear consistent with ITP.
10. 
Study participant at Screening has an IgG level of:
a.
>5.5g/L for non-splenectomized participants
b. ≥6.5g/L for splenectomized participants
Weight
11. 
Body weight >35kg at Screening.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 65 of 220
Sex
12a.
Study participants may be male or female:
−
A male participant must agree to use contraception as detailed in Appendix 4, 
Section 10.4 during the Treatment Period and for at least 3 months after the final dose of 
study treatment and refrain from donating sperm during this period.
−
A female participant is eligible to participate if she is not pregnant (see Appendix 4, 
Section 10.4) as confirmed by a negative serum pregnancy test and not planning to get 
pregnant during the participation in the study, not breastfeeding, and at least one of the 
following conditions applies:
◦
Not a woman of childbearing potential (WOCBP) as defined in Appendix 4, 
Section 10.4.
OR
A WOCBP who agrees to follow the contraceptive guidance in Appendix 4, 
Section 10.4 during the Treatment Period and for at least 3 months after the dose of 
study treatment.
Informed consent
13. Study participant must be capable of giving signed informed consent as described in 
Appendix 1, Section 10.1.3 which includes compliance with the requirements and restrictions 
listed in the Informed Consent Form (ICF) and in this protocol.
5.2
Exclusion criteria
Participants are excluded from the study if any of the following criteria apply:
Medical conditions
1. Study participant has any medical or psychiatric condition that, in the opinion of the 
investigator, could jeopardize or would compromise the study participant’s ability to 
participate in this study.
2a. Participant has a history of arterial or venous thromboembolism (eg, stroke, transient 
ischemic attack, myocardial infarction, deep vein thrombosis or pulmonary embolism) within 
the 6 months prior to randomization or requires current anticoagulant treatment (Table 5-1).
3. Study participant has clinically significant bleeding that warrants immediate platelet 
adjustment (eg, menorrhagia with significant drop in hemoglobin).
4. Study participant has a history of alcohol use or other substance use disorder within the 
previous 12 months of the Screening Visit.
5a. Study participant has a known hypersensitivity to any components of the study medication or 
any other anti-FcRn medications.
6. Study participant has a known history of hyperprolinemia, since 
.
7b. Study participant has evidence of a secondary cause of immune thrombocytopenia (clear 
association with other medical conditions, eg, untreated H. pylori infection, leukemia, 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 66 of 220
lymphoma, common variable immunodeficiency, systemic lupus erythematosus, autoimmune 
thyroid disease or is drug induced), participant has a multiple immune cytopenia (eg, Evan’s 
syndrome), etc. For Japan-specific regulations, see Appendix 8, Section 10.8.
8a. Study participant has a clinically relevant active infection (eg, sepsis, pneumonia, or abscess) 
in the opinion of the investigator, or had a serious infection (resulting in hospitalization or 
requiring parenteral antibiotic treatment) within 6 weeks prior to the first dose of IMP.
9. Study participant with a known tuberculosis (TB) infection, at high risk of acquiring TB 
infection, or latent tuberculosis infection (LTBI), or current/history of nontuberculous 
mycobacterial infection (NTMBI).
10. Study participant has a history of a major organ transplant or hematopoietic stem cell/marrow 
transplant.
11a.Study participant has any of the following active GI disorders: inflammatory bowel disease, 
GI ulceration or diverticulitis.
12. Study participant has experienced a clinically symptomatic GI bleed (positive hemoccult 
tests without any signs and symptoms of GI bleeding will not be considered as “clinically 
symptomatic”) in the last 6 months prior to the Screening Visit and/or has current gastritis or 
esophagitis and/or has a known risk for clinically relevant GI bleeding beyond ITP.
13. Study participant has experienced intracranial bleed in the last 6 months prior to the 
Screening Visit.
14. Study participant has a history of coagulopathy disorders other than ITP.
15. Criterion removed.
16. Splenectomized participant with past medical history of OPSI.
17a.Study participant with current or medical history of IgA deficiency, or a measurement of IgA 
<50mg/dL at the Screening Visit.
Prior/Concomitant therapy/procedures
18. Study participant who has received any blood or blood products within 2 weeks prior to the 
Baseline Visit.
19. Study participant has undergone a splenectomy in the 2 years prior to the Baseline Visit.
20b. Splenectomized participant without adequate vaccination against S. pneumoniae, 
N. meningitidis, and H. influenzae as evidenced by: 
-
a lack of documented vaccination records per local guidance, OR
-
have not completed required vaccinations (S. pneumoniae, H. influenzae, and 
N. meningitidis) per Section 8.2.6 during the Prolonged Screening Period
Note: For splenectomized participants without any prior vaccination against one or all of the 
above-mentioned bacteria please refer to Section 8.2.6 of the protocol.
For Japan-specific regulations, see Appendix 8, Section 10.8.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 67 of 220
21a. Study participant has received a live vaccination within 8 weeks prior to Day 1 (Baseline 
Visit); or intends to have a live vaccination during the course of the study or within 7 weeks 
following the final dose of IMP.
22. Criterion removed.
23a. Criterion removed.
24a. Study participant has been treated with prohibited immunosuppressants, biologics and other 
therapies within a timeframe shorter than detailed in Table 5-1. Medications as presented in 
Table 5-1 are prohibited during the study, unless required as rescue therapy (specified in 
Section 6.4.3) during the study.
Table 5-1:
Treatment-free periods for immunosuppressants, biologics, other 
therapies, and antiplatelet/anticoagulant agents
Generic name (commercial/trade name)
Period relative to Baseline Visit 
(regardless of route of administration)
Immunosuppressants
Cyclophosphamide
6 months
Pimecrolimus (Elidel®)
4 weeks
Vinca alkaloids (vincristine, vinblastine)
12 weeks
Biologics (monoclonal antibodies and fusion proteins)
Abatacept (CTLA 4-Ig) (Orencia®)
6 months
Belimumab (Benlysta™)
6 months
Golimumab (Simponi™)
6 months
Natalizumab (Tysabri®)
6 months
Ofatumumab (Arzerra®)
6 months
Rituximab (Rituxan®) and ocrelizumab
6 months or if more than 6 months and 
B cells have not returned to normal
TACI-Ig (Atacicept®)
10 months
Veltuzumab
6 months
Other biologics
3 months or within 5 half-lives prior to the 
Baseline Visit (whichever is longer)
Inebulizumab
6 months and B-cell counts are within 
normal range
Other
Intravenous immunoglobulin
4 weeks
Plasma exchange (PEX)
4 weeks
Anti-D
4 weeks
Romiplostim (Nplate®)
4 weeks
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 68 of 220
Generic name (commercial/trade name)
Period relative to Baseline Visit 
(regardless of route of administration)
Antiplatelets and Anticoagulants (eg, thrombin inhibitors, Vitamin K antagonists, factor 
inhibitors)a
Warfarin
2 weeks
Phenprocoumon
2 weeks
Acenocoumarol
2 weeks
Heparin
1 week
Clopidogrel
1 week
Salicylates (Aspirin)
1 week (enteric coated aspirin up to 
150mg daily allowed)
Dipyridamole
1 week
Prasugrel
1 week
Ticagrelor
1 week
Tirofiban
1 week
Abciximab
1 week
a This is not a complete list. The treatment free period relative to Baseline should be at least 5 half-lives from last 
dose, but a minimum of 1 week, whichever is longer.
Prior/Concurrent clinical study experience
25. Study participant has previously received rozanolixizumab in another clinical study.
26. Study participant has participated in another study of an investigational IMP (and/or an 
investigational device) within the previous 30 days prior to the Screening Visit or within 
5 half-lives prior to Baseline (whichever is longer) or is currently participating in another 
study of an investigational IMP (and/or an investigational device).
27. Criterion removed. 
Diagnostic assessments
28a.Study participant has absolute neutrophil count <1500 cells/mm3 at the Screening Visit.
29. Criterion removed.
30. Study participant has a partial thromboplastin time ≥1.5x upper limit of normal (ULN) or 
International Normalized Ratio (INR) ≥1.5 at the Screening Visit.
31a.Study participant has 12-lead ECG with changes considered to be clinically significant upon 
medical review at Baseline.
32a.Study participant has renal impairment, defined as:
−
Glomerular filtration rate (GFR) less than 45ml/min/1.73 m2 at the Screening Visit.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 69 of 220
33b.Study participant has 3.0xULN of any of the following: alanine aminotransferase (ALT), 
aspartate aminotransferase (AST), or alkaline phosphatase (ALP) at the Screening Visit.
−
If participant has >ULN for ALT, AST, or ALP that does not meet the exclusion limit at 
Screening, repeat the tests, if possible, prior to dosing to ensure there is no further 
ongoing clinically relevant increase. In case of a clinically relevant increase, inclusion of 
the participant must be discussed with the Medical Monitor.
−
For participants with a Baseline result >ULN for ALT, AST, ALP, or total bilirubin, a 
Baseline diagnosis and/or the cause of any clinically meaningful elevation must be 
recorded in the eCRF.
34a.Study participant has bilirubin >1.5xULN (unless confirmed Gilbert’s syndrome). If 
participant has elevations only in total bilirubin, fractionate bilirubin to identify possible 
undiagnosed Gilbert’s syndrome (ie, direct bilirubin <35%) at the Screening Visit.
35. Current unstable liver or biliary disease per investigator assessment defined by the presence 
of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, 
persistent jaundice, or cirrhosis. NOTE: with exception of stable hepatobiliary conditions 
(including Gilbert’s syndrome, asymptomatic gallstones).
36. Presence of hepatitis B surface antigen (HBsAg) at the Screening Visit.
37. Positive hepatitis C antibody test result at Screening or within 3 months prior to the IMP 
dose. NOTE: Study participant with a positive hepatitis C antibody due to prior resolved 
disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained.
38. Study participant tests positive for HIV at the Screening Visit.
39a. Study participant has a current or medical history of primary immunodeficiency.
40. Study participant has active neoplastic disease or history of neoplastic disease within 5 years 
of the Screening Visit (except for basal or squamous cell carcinoma of the skin or carcinoma 
in situ of the uterine cervix which has been definitively treated with standard of care 
approaches).
41a. Study participant has corrected QT interval for heart rate using Fridericia's formula (QTcF) 
>450msec (for male participants) or QTcF >470msec (for female participants) or QTcF 
>480msec in participants with bundle branch block at the Baseline Visit.
Other exclusions
42. Criterion removed.
43a. Study participant has planned major elective surgical procedure for the duration of their 
participation in the study.
44. For Japan specific regulations, see Appendix 8, Section 10.8.
5.3
Lifestyle restrictions
There are no lifestyle restrictions during the study unless deemed to interfere with compliance 
with the protocol as deemed by the investigator.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 70 of 220
5.4
Screen failures
Screen failures are defined as study participants who consent to participate in the clinical study 
but are not subsequently randomly assigned to study treatment. A minimal set of screen failure 
information is required to ensure transparent reporting of screen failure participants to meet the 
Consolidated Standards of Reporting Trials publishing requirements and to respond to queries 
from regulatory authorities. Minimal information includes demography, screen failure details, 
eligibility criteria, and any SAE.
Individuals who do not meet the platelet count criteria for participation in this study (screen 
failure) may be rescreened. Individuals who do not meet other criteria for participation in this 
study may be rescreened once. Additional rescreening of these individuals following upfront 
discussion with the Medical Monitor or Study Physician might be allowed. Rescreened study 
participants should be assigned a new participant number for rescreening.
If a study participant has isolated test results (specifically those mentioned in the inclusion or 
exclusion criteria) that are outside of the specific range but are clinically nonsignificant, the 
abnormal value may be rechecked at the discretion of the investigator, following discussion with 
the Medical Monitor or Study Physician.
Rescreening of study participants is separate from the repeating of individual tests.
Adequate vaccination for all splenectomized participants within 4 years prior to enrollment is 
preferred. However, non-vaccinated splenectomized study participants can receive vaccination 
during the Prolonged Screening Period. If a booster is due during the study, to avoid treatment 
interruption, the booster can be given ahead of the 5-year schedule if needed, also as part of the 
Prolonged Screening Period. Splenectomized participants who received vaccination during the 
Prolonged Screening Period, including those who received vaccination booster, can be 
randomized at a minimum 4 weeks after the last vaccination provided all other eligibility criteria 
are met. 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 71 of 220
6
STUDY TREATMENTS
Table 6-1:
Treatments administered
Study Treatment Name:
Rozanolixizumab
Placebo
Dosage formulation
Solution for infusion
Aqueous solution
Unit dose strength(s)/Dosage level(s):
 QW
 QW
 QW
0.9% sodium chloride 
aqueous solution 
(physiological saline, 
preservative free)
Volume matching the 
rozanolixizumab volume for 
the weight tier; QW
Route of administration
Subcutaneous infusion
Dosing instructions:
Study treatment will be administered as a sc infusion with an 
infusion pump at a 
. A fixed-unit dose across 
different body weight tiers, as presented in Table 1-2 will be 
applied. The study participant’s body weight at the Screening 
Visit will be used for the dose assignation. In the case of any 
blockage of the infusion, a suitable flush (eg, 0.9% sodium 
chloride) is allowed.
If the participant is unable to tolerate a 
may be used at the discretion of the clinical site 
personnel administering the infusion.
Packaging and labeling:
Rozanolixizumab will be 
provided in glass vials, will 
be labeled as required per 
country requirement.
hr=hour; QW=every week; sc=subcutaneous; w/v=weight/volume
Details on the rate of infusion and storage conditions are provided in the IMP Handling Manual.
6.1
Preparation, handling, storage, and accountability requirements
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study treatment received and that any discrepancies were 
reported and resolved before the use of the study treatment.
Only participants enrolled in the study may receive study treatment, and only authorized site 
staff may supply or administer study treatment. All study treatments must be stored in a secure, 
environmentally controlled, and monitored (manual or automated) area in accordance with the 
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03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 72 of 220
labeled storage conditions with access limited to the unblinded authorized site staff or pharmacy 
staff.
The investigator or designee is responsible for study treatment accountability, reconciliation, and 
record maintenance (ie, receipt, reconciliation, and final disposition records).
In case an out-of-range temperature is noted, it must be immediately reported as per instructions 
contained in the IMP Handling Manual.
Further guidance and information for the final disposition of unused study treatment are provided 
in the IMP Handling Manual.
6.1.1
Drug accountability
A Drug Accountability form will be used to record IMP dispensing and return information on a 
by-participant basis and will serve as source documentation during the course of the study. 
Details of any IMP lost, damaged (due to breakage or wastage), not used, partially used, 
disposed of at the study site, or returned to the sponsor or designee must also be recorded on the 
appropriate forms. All supplies and pharmacy documentation must be made available throughout 
the study for UCB (or designee) to review.
UCB is responsible for retaining all used, unused, and partially used containers of IMP until 
returned or destroyed.
The investigator may assign some of the investigator’s duties for drug accountability at the study 
site to an appropriate qualified person and/or pharmacist/designee.
The investigator must ensure that the IMP is used only in accordance with the protocol.
Periodically, and/or after completion of the clinical phase of the study, all used (including empty 
containers)/partially used, unused, damaged, and/or expired IMP must be reconciled and either 
destroyed at the site according to local laws and regulations considering UCB standard operating 
procedures (SOPs) or returned to UCB (or designee). IMP intended for the study cannot be used 
for any other purpose than that described in this protocol.
6.2
Measures to minimize bias: randomization and blinding
An interactive response technology (IRT) will be used for assigning eligible study participants to 
a treatment regimen (as applicable) based on a predetermined production randomization and/or 
packaging schedule provided by UCB (or designee). The randomization schedule will be 
produced by the IRT vendor. The IRT will generate individual assignments for kits of IMP, as 
appropriate, according to the visit schedule.
To enroll a study participant (Screening Visit), the investigator or designee will contact the IRT 
and provide brief details about the participant to be enrolled. Each participant will receive a 
5-digit number assigned at Screening that serves as the participant identifier throughout the 
study. The participant number will be required in all communication between the investigator or 
designee and the IRT regarding a particular study participant. Participant numbers and kit 
numbers will be tracked via the IRT.
To randomize a study participant, the investigator or designee will contact the IRT and provide 
brief details about the participant to be randomized. The IRT will automatically inform the 
investigator or designee of the participant’s randomization. The IRT will allocate kit numbers to 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
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the participant based on the participant number during the course of the study. The 
randomization number will be incorporated from the IRT into the eCRF by automatic data 
transfer.
The randomization will be stratified by the following:
•
Degree of thrombocytopenia (platelet count < or ≥15×109/L)
•
Splenectomy: yes/no
6.2.1
Procedures for maintaining and breaking the treatment blind
6.2.1.1
Maintenance of study treatment blind
All study participant treatment details, rozanolixizumab treatment arm, planned dose, or placebo,
will be allocated and maintained by the IRT system.
Study site pharmacists or other suitably qualified site personnel who are responsible for 
preparations of the IMP will be unblinded as they have access to treatment allocations for 
individual participants via the IRT. The unblinded pharmacy monitors from the contract research 
organization (CRO), the Clinical Supply Manager, and the unblinded Clinical Project Manager 
(CPM) (or designee) will also have access to the treatment allocations and to the drug 
accountability records, if applicable.
The following individuals may, as necessary, have access to the treatment allocations for 
individual participants via the IRT:
•
Sponsor Patient Safety (PS) staff as needed for reporting SAEs to regulatory authorities.
•
Members of the IDMC who participate in unblinded sessions will be given information about 
the IMP allocation for those participants for whom data are provided at these sessions.
•
Sponsor and/or CRO staff supporting preparation of the data outputs for the IDMC review 
and/or any interim analyses.
•
A Quantitative Clinical Pharmacologist/Modeling and Simulation Scientist may have access 
to the randomization code if PK data are requested for review by the IDMC.
•
The bioanalytical scientific manager (or designee)
An independent Quantitative Clinical Pharmacologist/Modeling and Simulation Scientist may 
have access to the randomization code to review unblinded PK, platelet and serum IgG data. 
All study participant treatment details will be allocated and maintained by the IRT system.
For safety reasons, the blinded investigator (or designee) has to receive and review the platelet 
counts from the local laboratory, which will be documented by the blinded site personnel in the 
eCRF. An increase in platelet count during the Treatment Period is not considered as an 
unblinding. As such, an increase in platelet count is expected for approximately 60% of the study 
participants, and up to 10% of placebo-treated study participants may experience an increase in 
platelet count. Platelet counts may be shared with study participants as this is deemed necessary 
information for participants when engaging in activities of daily living. 
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03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 74 of 220
Unintentional formal unblinding occurs when the unblinded study site pharmacists or other 
suitably qualified site personnel responsible for IMP preparation share the treatment allocations 
for individual participants (or equivalent information) with the blinded site personnel 
accidentally. The same applies to the blinded sponsor and/or CRO staff.
Unintentional informal unblinding of the blinded investigator (or designee) and the blinded site 
personnel is only applicable if IgG levels are shared by the central laboratory in error. Given the 
pharmacological property of the IMP, a change of IgG level may be suggestive of a treatment 
effect however, does not disclose the treatment allocation.
To maintain the study integrity, study site personnel, the UCB and CRO study teams will remain 
blinded to IgG levels. However, to ensure study participants’ safety, serum IgG level will be 
monitored by unblinded Medical Monitors external to UCB. In case the serum IgG level 
decreases <1g/L, the unblinded Medical Monitors will inform the investigator as described in 
Table 10-8. Potential actions to be taken may include maintaining the dose, reducing the dose or 
initiation of mock infusions. Temporary treatment discontinuation due to low IgG levels may 
informally unblind the treatment assignment to the participant. Therefore, infusions will be 
continued but given as mock infusions with only placebo irrespective of IMP designation. 
Allocation of mock kit numbers will be handled via the IRT. Refer to Appendix 25, 
Section 10.25 for further information.
Further details are provided in the study manual and site blinding plan. 
6.2.1.2
Breaking the treatment blind in an emergency situation
In the event of an emergency, it will be possible to determine to which treatment arm and dose 
the study participant has been allocated by contacting the IRT. At the start of the study, all sites 
will be provided with details of how to contact the system for code breaking. The Medical 
Monitor or equivalent should be consulted prior to unblinding, whenever possible.
The CPM will be informed immediately via the IRT when a code is broken but will remain 
blinded to specific treatment information. Any unblinding of the IMP performed by the 
investigator must be recorded in the source documents and on the Study Termination eCRF page.
6.3
Treatment compliance
During the Treatment Period, IMP will be administered at the clinical site or study participant’s 
home as a sc infusion by a qualified designee. Drug accountability must be recorded on the Drug 
Accountability form (see Section 6.1.1).
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03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
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Page 75 of 220
6.4
Concomitant medication(s)/treatment(s)
6.4.1
Permitted concomitant treatments (medications and therapies)
The following concomitant medications are permitted during the study and if possible, kept 
stable for the duration of the study (Table 6-2):
Table 6-2:
Permitted concomitant treatments (medications and therapies)
Permitted Medications
Dose
Commenta
Oral corticosteroids 
≤20mg/day
(prednisone equivalent dose)
Stable dose for 
 prior to 
Baseline
Mycophenolate mofetil
≤3g/day
Stable dose for 
 prior to 
Baseline
Cyclosporin
≤5mg/kg/day for unmodified
≤4mg/kg/day for modified
Stable dose for 
 prior to 
Baseline
Azathioprine
≤3mg/kg/day
Stable dose for 
 prior to 
Baseline
Danazol
≤15mg/kg/day
Stable dose for 
 prior to 
Baseline
Dapsone
100mg/day
Stable dose for 
 prior to 
Baseline
Eltrombopag, 
Avatrombopag
Any dose
Stable dose for 
 prior to 
Baseline
Fostamatinib
Any dose
Stable dose for 
 prior to 
Baseline
a Stable dose is defined as either the same dose and frequency of the respective medication taken for the period of 
time defined in Table 6-2, or no dose of the respective medication taken for the period of time as defined in 
Table 6-2.
The use of medicinal cannabidiols and medicinal marijuana (prescribed by a physician) is also 
permitted. When applicable, the study participant must be on a stable dose of cannabidiols and/or 
medicinal marijuana for 
 prior to Screening and remain stable for the duration of the 
study. For Japan-specific regulations, see Appendix 8, Section 10.8.
6.4.2
Prohibited concomitant treatments (medications and therapies)
The following concomitant medications are prohibited during the study:
•
IVIg (unless given as a rescue therapy)
•
All biologics including rituximab
•
Cyclophosphamide
•
Pimecrolimus
•
PEX 
•
Immunoadsorption 
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03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
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•
Anti-D
•
Any systemically administered corticosteroids above the allowed background dose (unless 
required as a rescue therapy)
•
Romiplostim 
•
Vinca alkaloids (vincristine, vinblastine)
•
Anticoagulants and antiplatelets (warfarin, heparin, clopidogrel, aspirin [enteric coated up to 
150mg daily allowed], salicylics, dipyridamole, prasugrel, ticagrelor, tirofiban, and 
abciximab).
For study participants who require a medical or surgical procedure that requires the use of 
general anesthesia, discussion must occur prior to the procedure with the Medical Monitor or 
study physician, such that a decision on the participant's continued participation in the study can 
be made. In an emergency situation, the discussion should occur as soon as possible after the 
procedure. 
The use of prohibited concomitant treatment will lead to permanent discontinuation from IMP. 
Study participants should then complete the assessments outlined for the Early Withdrawal (EW) 
Visit and enter the SFU Period.
6.4.3
Rescue therapy
Rescue treatment will be given as per standard of care and at the discretion of the investigator as 
described below. If such rescue therapy is given, the participant is allowed to continue IMP 
treatment (as per guidance below), and should continue to complete all remaining scheduled 
visits in the Treatment Period, as per the Schedule of Activities (Section 1.3). The following 
rescue therapies may be used:
•
Any increase in concomitant ITP therapies above Baseline dose
•
Any additional ITP medication/therapies including but not limited to:
−
Platelet transfusion (only in cases of severe bleeding)
−
Commercially available IVIg
−
Any systemically administered corticosteroids (above the background doses, ie, pulse, 
oral and iv steroids). Any systemic corticosteroids used for the management of infusion 
reactions or other medical conditions are also considered rescue therapy.
−
Immunosuppressants (except for those listed in Section 6.4.2).
Although the use of rescue therapy is allowable at any time during the study, the use of rescue 
therapy should be delayed, if possible, for at least 2 days following the administration of study 
treatment.
If IVIg, high dose corticosteroids, or platelet transfusion are given as rescue therapy, IMP 
treatment can commence at the same dose as previously when platelet counts are <50×109/L. 
Dose can be up-titrated at a later timepoint, if needed, depending on platelet level.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 77 of 220
A high dose of corticosteroids is defined as any iv administration of corticosteroids given for any 
reason or doubling of an oral dose resulting in a dose more than 20mg/day prednisone equivalent 
dose.
In case of an increase of Baseline oral corticosteroids, not resulting in doubling of the oral dose 
more than 20mg/day prednisone equivalent dose, an increase in the concomitant ITP therapies 
above Baseline, or in case of administration of immunosuppressants as rescue therapy, IMP 
administration can continue as per Schedule of Activities (Section 1.3) at a dose adjusted 
depending on the platelet level.
The date and time of rescue therapy administration as well as the name and dosage regimen of 
the rescue therapy must be recorded in the eCRF.
6.5
Dose modification
Dose modifications of the IMP are permitted in order to maintain the platelet counts between 
≥50×109/L and ≤150×109/L (Table 1-1 and Figure 1-1). 
Dose modifications or temporary discontinuation of the IMP treatment are permitted if serum 
IgG value is <1g/L (Section 10.25).
In the event of treatment-related AEs, other than those that meet the IMP discontinuation criteria 
(as defined in Section 7.1) a dose reduction is permitted. Treatment-related AEs due to which 
dose modifications are recommended may include, but are not limited to:
•
Moderate to severe headaches 
•
Severe vomiting and diarrhea 
•
Moderate to severe toxicities (Grade 2 and above, as defined by Common Terminology 
Criteria for Adverse Events version 5.0) for which rozanolixizumab cannot be excluded as a 
cause
6.6
Treatment after the end of the study
Study participants (regardless of whether they receive rescue therapy), upon completion of the 
Treatment Period and if fulfilling the eligibility criteria, will be given the opportunity to enroll 
into the OLE study, TP0004.
In case the enrollment into TP0004 is not conducted at Week 25 (Visit 27), a visit window of +3 
days will be granted; therefore, rollover into TP0004 needs to be completed +3 days after 
Week 25 at the latest.
For study participants not enrolling into the OLE study, there are no plans for continued 
provision of rozanolixizumab after the end of the study. The participant should discuss any 
alternative treatment options (if needed after the study) with their healthcare provider.
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03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 78 of 220
7
DISCONTINUATION OF IMP AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1
Discontinuation of IMP
7.1.1
Liver chemistry stopping criteria
Discontinuation of study treatment for abnormal liver function should be considered by the 
investigator when a study participant meets one of the conditions outlined in Figure 7-1 and 
Figure 7-2, or if the investigator believes that it is in the best interest of the participant.
Figure 7-1:
Liver chemistry stopping criteria and increased monitoring algorithm
ALT=alanine transaminase; AST=aspartate aminotransferase; INR=international normalized ratio; SAE=serious 
adverse event; ULN=upper limit of normal
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 79 of 220
Figure 7-2:
Liver chemistry increased monitoring algorithm with continued study 
intervention for participants with ALT ≥3xULN but <8xULN
ALT=alanine transaminase; AST=aspartate aminotransferase; bili=bilirubin; INR=international normalized ratio; 
SAE=serious adverse event; ULN=upper limit of normal
Specific assessments and follow-up actions for potential drug-induced liver injury (PDILI) are 
provided in Appendix 6, Section 10.6.
7.1.2
QTc stopping criteria
If a clinically significant finding is identified (including but not limited to: changes from 
Baseline in QT interval corrected using Fridericia’s formula) after enrollment, the investigator or 
qualified designee will determine if the study participant can continue in the study and if any 
change in participant management is needed. This review of the ECG printed at the time of 
collection must be documented. Any new clinically relevant finding should be reported as an AE.
A study participant who meets the bulleted criteria based on the ECG readings will discontinue 
IMP and move into the SFU Period. The study participant should be referred to a specialist (ie, 
cardiologist) and managed as per local guidance.
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QTc >500 msec OR uncorrected QT >600 msec
•
Change from Baseline of QTc >60 msec
For study participants with underlying bundle branch block, follow the discontinuation criteria 
listed below:
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 80 of 220
Baseline QTc with Bundle Branch Block
Discontinuation QTc Threshold with Bundle 
Branch Block
<450 msec
>500 msec
450 to 480 msec
≥530 msec
7.1.3
Discontinuation of IMP due to other adverse events or medical 
condition
Study participants MUST permanently discontinue IMP and move into the SFU Period if any 
of the following events occur:
−
Study participant has a significant infective episode including but not limited to: 
bacteremia or sepsis, infectious meningitis, osteomyelitis, septic arthritis, complicated 
pneumonia or visceral abscess which may or may not result in hospitalization. This list is 
not intended to be all inclusive, and the investigator is expected to apply his/her judgment 
on continuing IMP based on the clinical situation at hand (see Appendix 25, 
Section 10.25).
−
Study participant has new onset or recurrent neoplastic disease (except for superficial 
basal or squamous cell carcinoma of the skin not requiring targeted biological therapy, 
chemotherapy or radiation).
−
Study participant has an AE of severe or serious hypersensitivity, infusion related 
reaction (see Appendix 24, Section 10.24) or anaphylaxis requiring corticosteroid and/or 
epinephrine therapy (see Appendix 21, Section 10.21) (Sampson et al, 2006).
−
Study participant has a serious AE of headache or GI disturbance that is considered 
related to the IMP in the opinion of the investigator; or recurrent severe AE of headache 
(see Appendix 22, Section 10.22) or GI disturbance that is considered related to the IMP 
in the opinion of the investigator (See Appendix 23, Section 10.23).
−
Study participant has a life-threatening bleeding event.
−
Study participant has an AE of arterial or venous thromboembolic event (eg stroke, 
myocardial infarction, pulmonary embolism, deep vein thrombosis).
−
Study participant has evidence suggestive of potential TB infection (eg, exposure), and 
further examinations result in a diagnosis of active TB, LTBI, or NTMBI (see 
Section 8.2.5). 
−
If a NTMBI is identified during the study, the same withdrawal procedures as those used 
for an active TB infection identified during the study should be followed.
Study participants who permanently discontinue IMP during the Treatment Period and hence are 
withdrawn from the study should complete the assessments outlined for the Early Withdrawal 
(EW) Visit and enter the SFU Period.
7.1.4
Temporary IMP discontinuation
Study participant MUST temporarily discontinue IMP if any of the following events occur:
1. Thrombocytosis (platelet count of ≥400×109/L).
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03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 81 of 220
2. In the event of confirmed COVID-19 infection (eg, signs/symptoms such as fever, cough, 
shortness of breath), or known exposure sufficient to necessitate testing or self-imposed 
quarantine. 
The IMP may be restarted if:
a. COVID-19 test is negative, and signs and symptoms have resolved
b. If test is not available, resolution of signs and symptoms and 14 days have passed since 
initial presentation of the clinical signs/symptoms. 
c. If asymptomatic, 14 days have elapsed since known exposure. 
Study participant MAY temporarily discontinue IMP if any of the following events occur:
1. A severe AE of headache that is considered related to the IMP in the opinion of the 
investigator (Section 10.22)
2. A splenectomised study participant develops a (persistent or re-occurring) nonserious 
infection, as per investigator’s decision (Section 10.25)
3. Total serum IgG value is <1g/L as per investigator’s decision. As IMP treatment is 
administered weekly, the decision to temporarily hold the treatment should be determined 
based on the most recently available total IgG value. As the IgG, IgG subtypes, albumin and 
total protein levels will be blinded to both the study site personnel and the clinical team at the 
sponsor and CRO, unblinded Medical Monitors will be monitoring the IgG levels and will 
alert the investigator in case of decreases <1g/L. Additionally, guidance for investigators on 
management of infections can be found in Appendix 25, Section 10.25.
7.2
Participant discontinuation/withdrawal from the study
Study participants are free to withdraw from the study at any time, without prejudice to their 
continued care. Participants who withdraw from the study should complete the EOS Visit.
A study participant may also be withdrawn from the study at any time at the discretion of the 
investigator for safety, behavioral, compliance, or administrative reasons.
If the study participant withdraws consent for disclosure of future information, the sponsor may 
retain and continue to use any data collected before such a withdrawal of consent.
If a study participant withdraws from the study, he/she may request destruction of any samples 
taken and not tested, and the investigator must document this in the site study records.
See the Schedule of Activities (Section 1.3) for data to be collected at the time of study 
discontinuation and follow up and for any further evaluations that need to be completed.
Study participants must be withdrawn from the study and permanently discontinued from IMP if 
any of the following events occur:
1. Study participant withdraws his/her consent.
2. Study participant takes prohibited concomitant medications as defined in this protocol.
3. Study participant meets the mandatory IMP discontinuation criteria as per Section 7.1.1,
Section 7.1.2 or Section 7.1.3.
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03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 82 of 220
4. There is confirmation of a pregnancy during the study, as evidenced by a positive pregnancy 
test.
5. The sponsor or a regulatory agency requests withdrawal of the study participant.
Study participants who withdraw from the study or permanently discontinue IMP during the 
Treatment Period should complete the assessments outlined for the EW Visit, enter the SFU 
Period and complete the EOS Visit. 
Investigators should contact the Medical Monitor, whenever possible, to discuss the withdrawal 
of a participant in advance. Study participants who are withdrawn will not be replaced.
7.3
Lost to follow up
A study participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a study participant fails to return to the clinic for a 
required study visit:
•
The site must attempt to contact the study participant and reschedule the missed visit as soon 
as possible and counsel the study participant on the importance of maintaining the assigned 
visit schedule and ascertain whether or not the participant wishes to and/or should continue in 
the study.
•
Before a study participant is deemed lost to follow up, the investigator or designee must 
make every effort to regain contact with the participant (at least 1 phone call and 1 written 
message to the participant), and document his/her effort (date and summary of the phone call 
and copy of the written message) in the source documents. 
Should the study participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up documented in the eCRF.
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03 Dec 2021
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Rozanolixizumab
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Page 83 of 220
8
STUDY ASSESSMENTS AND PROCEDURES
Study procedures and their timing are summarized in the Schedule of Activities (Section 1.3).
Protocol waivers or exemptions are not allowed.
Immediate safety concerns should be discussed with the sponsor (or designee - Medical Monitor 
at CRO) immediately upon occurrence or awareness to determine if the participant should 
continue or discontinue study treatment.
Adherence to the study design requirements, including those specified in the Schedule of 
Activities (see Section 1.3), is essential and required for study conduct.
All Screening evaluations must be completed and reviewed to confirm that potential participants 
meet all eligibility criteria. Screening assessments can be performed on different days throughout 
the Screening Period, if required. The investigator will maintain a Screening log to record details 
of all participants screened and to confirm eligibility or record reasons for Screening failure, as 
applicable.
Procedures conducted as part of the participant’s routine clinical management (eg, blood count) 
and obtained before signing of the ICF may be utilized for Screening or Baseline purposes 
provided the procedures met the protocol-specified criteria and were performed within the time 
frame defined in the Schedule of Activities (see Section 1.3).
An Unscheduled Visit can be conducted at the discretion of the investigator (eg, due to an AE).
During the Unscheduled Visit, the following assessments will be performed:
•
AE reporting
•
Concomitant medications 
•
Review of withdrawal criteria
•
Physical examination
•
Vital signs
•
Blood samples for PK, IgG, hematology, biochemistry, other testing such as for TB or 
C-reactive protein (CRP) as clinically indicated in the opinion of the investigator.
Other assessments may be performed at the discretion of the investigator.
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the 
samples.
Some study-specific investigations may not be conducted according to the study protocol during 
a pandemic or other exceptional circumstances (eg, hurricanes) due to the need to implement 
safety measures and guidance from regulatory authorities. In such a situation, which may be 
accompanied by local or global containment or other measures, sites may need to prohibit access 
to study participants and study-related personnel. Study participant visits to the study site may be 
replaced by contingency measures. These measures are primarily established to ensure the safety 
of study participants during the course of the study and to maintain the study participants 
treatment schedule, if the investigator considers it appropriate. These measures include but are 
not limited to virtual visits or home-nursing visits replacing site visits, eg, telemedicine contacts 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 84 of 220
or home-nursing visits when treatment and/or blood sampling is scheduled. The contingency 
measures are described in a contingency plan which will be maintained by UCB for the 
respective study. The contingency measures are shared with the investigator and the respective 
study-related personnel as soon as there are indications that it is necessary to implement any of 
the measures.
The participant may have the option to have home-nursing visits as specified in Section 1.3.
Home-nursing visits will be conducted by 2 fully trained healthcare professionals (1 unblinded 
for IMP preparation and 1 blinded for the other assessments) visiting the participant at his/her 
home or other locations (eg, rehabilitation or day care centers, etc). Alternatively, these visits can 
be conducted at the site as deemed necessary by site personnel and/or participant, or when home-
nursing visits are not available. Where dosing is performed at home or at other locations, the
same safety monitoring schedule will be followed as in the clinic. These healthcare professionals 
will be present during the full duration of the visit. Home visits and visits at other locations can 
be conducted in case the following conditions are met:
•
The participant is willing to be dosed and monitored at home, or at an alternative location by 
healthcare professionals.
•
The participant has shown good acute tolerability to previous administrations of IMP 
(namely they must have had no moderate or severe infusion reactions, or other AEs which 
the investigator considers could increase the risk of home administration).
•
The participant does not require specific medical supervision based on their medical 
history/condition.
•
The team delivering the home dose must be trained in the identification and management of 
infusion reactions and hypersensitivity and must have access to immediate treatments (eg, an 
EpiPen or adequate alternative).
•
The participant’s home or alternative location allows rapid access to emergency treatment if 
required (ie, the participant must not live so remotely that a reasonable arrival time of an 
ambulance could not be predicted).
•
The investigator or site designee is contactable to support the healthcare provider if needed.
•
UCB has not requested to limit the possibility to perform home visits or visits at other 
locations (eg, based on IDMC recommendation).
The investigator will be asked to complete a checklist confirming all criteria have been fully
evaluated. This checklist will be shared with the UCB study physician or designee and reviewed
before the first home visit for IMP administration can take place.
8.1
Efficacy assessments
8.1.1
Platelet counts
For assessment of platelet counts, blood samples will be collected by qualified site personnel at 
the same time that samples are collected for standard clinical laboratory assessments. The time 
and date of the blood draws will be recorded in medical source data and the eCRF. Assessment 
will be performed according to the Schedule of Activities (Section 1.3).
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03 Dec 2021
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Platelet counts will be determined by a local laboratory and the following endpoints will be 
derived for the purpose of analysis:
•
Durable Clinically Meaningful Platelet Response of ≥50×109/L, for at least 8 out of 12 weeks 
during the last 12 weeks (Week 13 to 25)
•
Cumulative number of weeks with Clinically Meaningful Platelet Response defined as: 
platelet count ≥50×109/L over the 24-week treatment period
•
Time to first Clinically Meaningful Platelet Response of ≥50×109/L defined as: time from 
starting treatment to achievement of first response of ≥50×109/L
•
Clinically Meaningful Response defined as ≥50×109/L by Day 8
•
Response defined as platelet count ≥30×109/L and at least a 2-fold increase of the Baseline 
count confirmed on at least 2 separate occasions at two adjacent nominal visits at least 7 days 
apart, and absence of bleeding by visit 
•
Time to first Response defined as: time from starting treatment to achievement of Response
•
Duration of first Clinically Meaningful Platelet Response of <50×109/L: measured from 
achievement of first Response to loss of first Response (loss of Response defined as platelet 
count <50×109/L)
•
Complete Response defined as platelet count ≥100×109/L confirmed on at least 2 separate 
occasions at two adjacent nominal visits at least 7 days apart, and absence of bleeding by 
visit
•
Cumulative number of weeks over the planned 24-week treatment period with a platelet 
count of ≥100×109/L 
•
Cumulative number of weeks over the planned 24-week treatment period with platelet counts 
≥30×109/L and at least doubling from Baseline
•
Mean change from Baseline in platelet count by visit
•
Clinically Meaningful Platelet Response of ≥50×109/L, for at least 4 out of 6 weeks during 
the last 6 weeks (Week 19 to 25)
•
Clinically Meaningful Platelet Response of ≥50×109/L, for at least 6 out of 8 weeks during 
the last 8 weeks (Week 17 to 25)
The Response and Complete Response variables will be assessed only for visits for which both 
platelet counts and the ITP bleeding score are assessed (with the exception of the confirmatory 
platelet assessments which may be obtained at any visit (scheduled or unscheduled) provided 
that they meet the criteria below). In order to define a Response (platelet count ≥30×109/L), the 
platelet count must be confirmed on 2 separate occasions and in the absence of bleeding. The 
time to first Response will be taken as the time to the first platelet assessment (obtained at the 
same time as the corresponding ITP bleeding score assessment). If the second assessment does 
not fulfill the required criteria for a Clinical Response, the study participant will be considered as 
a nonresponder at the respective visits. Further details will be provided in the Statistical Analysis 
Plan (SAP). 
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03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
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Confidential
Page 86 of 220
Refer to Section 9.3 for details of statistical analysis of these variables.
8.1.2
ITP bleeding score
The International Working Group on ITP proposes a consensus-based ITP-BAT, based on a 
precise definition of bleeding manifestations and on the grading of their severity (Rodeghiero et 
al, 2013). The ITP bleeding score will be assessed using the ITP-BAT tool Version 1.0. 
Assessment will be performed according to the Schedule of Activities (Section 1.3).
For the ITP-BAT, bleeding manifestations were grouped into 3 major domains: S, M, and O, 
with the skin, mucosae, organs with grading of severity (SMOG) system. Each bleeding 
manifestation is assessed at the time of examination. Severity is graded from 0 to 3 or 4, with 
Grade 5 for any fatal bleeding. Absence of bleeding will correspond to a Grade 0 or 1 for Skin 
and Grade 0 for Mucosae or Organ domains. Presence of bleeding is indicated by a Mucosae or 
Organs Grade ≥1, or Skin Grade ≥2. Bleeding reported by the participant without medical 
documentation is Graded 1. Within each domain, the same grade is assigned to bleeding 
manifestations of similar clinical impact. The “worst” bleeding manifestation since the last visit 
is graded, and the highest grade within each domain is recorded. The SMOG system provides a 
consistent description of the bleeding phenotype in ITP.
A standardized data collection form will be used to facilitate collection of information and 
communication among physicians and investigators. The grading of bleeding symptoms at 
presentation and at each subsequent evaluation is presented in Appendix 12, Section 10.12.
8.1.3
Patient Reported Outcomes
Patient reported outcomes must be completed as per time points mentioned in the Schedule of 
Activities (Section 1.3). The PROs should be completed prior to any intrusive procedures in a 
quiet place. On dosing days, PROs will be completed prior to dosing.
The PROs should be completed in the following order: ITP-PAQ, SF-36, the FATIGUE-PRO 
Physical Fatigue Scale, EQ-5D-5L, PGI-S, and PGI-C.
8.1.3.1
ITP-PAQ
The ITP-PAQ is a 44-item disease-specific Health-Related Quality of Life (HRQoL) 
questionnaire developed for use in adults with chronic ITP. It includes 11 scales: Symptoms, 
Fatigue, Physical Health – Bother, Physical Health – Activity, Emotional Health –
Psychological, Emotional Health – Fear, Overall QoL, Social Activity, Women’s Reproductive 
Health – Fertility, Women’s Reproductive Health - Menstrual Symptoms, and Work. Each item 
is rated on a Likert-type scale containing 4 to 7 responses. All item scores are transformed to a 0 
to 100 continuum and are weighted equally to derive individual scale scores. Higher scores 
indicate better health status (Mathias et al, 2009; Mathias et al, 2007).
The ITP-PAQ Symptoms score was selected as secondary efficacy endpoint for the study to 
capture the benefits of rozanolixizumab in terms of patient-perceived symptoms. It covers 6 core 
symptoms of ITP: bruising/petechiae, wounds/scars (from blood tests, injections or IV needles), 
blood blisters in mouth, bleeding episodes, muscle aches, and cramps in legs.
The ITP-PAQ sample questionnaire is available in Appendix 13, Section 10.13.
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03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
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8.1.3.2
SF-36
Study participants will complete the SF-36 questionnaire according to the Schedule of Activities 
(see Section 1.3). The SF-36 sample questionnaire is available in Appendix 14, Section 10.14.
8.1.3.3
FATIGUE-PRO Physical Fatigue Scale
The FATIGUE-PRO Physical Fatigue scale is one of the three scales of the broader
FATIGUE-PRO instrument developed by UCB. It consists of 9 items rated on a 5-point 
frequency response scale ranging from "none of time" to "all of the time", with a 7-day recall 
period. The FATIGUE-PRO Physical Fatigue score ranges 0 to 100, with higher score meaning 
more physical fatigue.
The FATIGUE-PRO Physical Fatigue scale is available in Appendix 15, Section 10.15.
8.1.3.4
EQ-5D-5L
The EQ-5D-5L is designed to improve the instrument’s sensitivity and to reduce ceiling effects.
The EQ-5D-5L consists of 2 pages: the EQ-5D descriptive system and the EuroQol visual 
analogue scale (EQ VAS).
The descriptive system comprises 5 dimensions: mobility, self-care, usual activities, 
pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight 
problems, moderate problems, severe problems, and extreme problems. The study participant is 
asked to indicate his/her health state by ticking the box next to the most appropriate statement in 
each of the 5 dimensions. This decision results in a 1-digit number that expresses the level 
selected for that dimension. The digits for the 5 dimensions can be combined into a 5-digit 
number that describes the study participant’s health state.
The EQ-VAS records the study participant’s self-rated health on a vertical visual analogue scale, 
where the endpoints are labelled ‘The best health you can imagine’ and ‘The worst health you 
can imagine’. The VAS can be used as a quantitative measure of health outcome that reflect the 
study participant’s own judgment.
Study participants will complete the EQ-5D-5L questionnaire according to the Schedule of 
Activities (see Section 1.3). The EQ-5D-5L sample questionnaire is available in Appendix 16, 
Section 10.16.
8.1.3.5
PGI-S
The PGI-S is a single-state, self-report measure that rates a study participant's severity of a 
specific condition. The PGI-S is a 5-point scale depicting a study participant's rating of overall 
symptoms (“none,” “mild,” “moderate,” “severe,” or “very severe”). 
The PGI-S sample questionnaire is available in Appendix 17, Section 10.17.
8.1.3.6
PGI-C
The PGI-C is a single-state, self-report measure that reflects a study participant's belief about the 
efficacy of treatment for a specific condition. The PGI-C is a 7-point scale depicting a study 
participant's rating of overall improvement (“very much improved,” “much improved,” 
“minimally improved,” “no change,” “minimally worse,” “much worse,” or “very much worse”).
The PGI-C sample questionnaire is available in Appendix 18, Section 10.18.
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03 Dec 2021
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8.2
Safety assessments
Planned time points for all safety assessments are provided in the Schedule of Activities 
(Section 1.3).
8.2.1
Physical examination
A full physical examination will include, at a minimum, assessments of general appearance; ear, 
nose, and throat; eyes, hair, and skin; assessments of the cardiovascular, respiratory, GI, 
neurological, musculoskeletal, and hepatic systems; and mental status.
A short physical examination will include, at a minimum, assessments of general appearance; 
ear, nose, and throat; skin, respiratory, GI, and neurological systems.
For full and short physical examinations, investigators should pay special attention to clinical
signs related to previous serious illnesses as well as signs and symptoms of infections.
Clinically relevant findings or worsening of previous findings will be recorded as AEs.
8.2.2
Vital signs
Oral, tympanic, or axillary temperature, pulse rate, and BP will be assessed.
Blood pressure (systolic and diastolic) and pulse rate measurements should be preceded by at 
least 5 minutes of rest for the study participant in a quiet setting without distractions (eg, 
television, cell phones). All measurements will be assessed in a sitting position with a completely 
automated device. Manual techniques will be used only if an automated device is not available.
All vital signs should be taken before any blood sampling.
On dosing days, for the first 2 weeks, vital signs will be measured prior to IMP administration, at 
the end of the infusion, and 4 hours after the end of the infusion. For the next 3 visits, vital signs 
will be measured prior to IMP administration, at the end of infusion, and 1 hour after the end of 
infusion. From Week 6, vital signs will be measured prior to IMP administration, at the end of 
the infusion, and 15 minutes after the end of infusion. At nondosing visits, vital signs need only 
to be taken once during the visit. In case of dose increase, vital signs will be measured prior to 
IMP administration, at the end of infusion, and 1 hour after the end of infusion for the next 
2 infusions. In case of an untoward event, additional vital signs (unscheduled assessment) should 
be taken at the discretion of the investigator and post-observation time can be extended. These 
recommendations are applicable for dosing at site and at home.
8.2.3
Electrocardiograms
A 12-lead ECG will be obtained as outlined in the Schedule of Activities (see Section 1.3) using 
an ECG machine that automatically calculates the heart rate and measures pulse rate, QRS, QT, 
and QTc intervals.
Central reading of ECGs will be performed but for the assessment of the ECG during the visit, 
the assessment of the investigator or designee will be used to determine eligibility and 
continuation in the study.
All ECG recordings should be taken prior to blood collection for assessment of laboratory 
parameters, with the study participant resting in the supine position for at least 5 minutes before 
the recording.
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03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
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8.2.4
Clinical safety laboratory assessments
See Appendix 2, Section 10.2 for the list of clinical laboratory tests to be performed and to the 
Schedule of Activities (Section 1.3) for the timing and frequency.
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the eCRF. The 
laboratory reports must be filed with the source documents. Clinically significant abnormal 
laboratory findings are those which are not associated with the underlying disease, unless judged 
by the investigator to be more severe than expected for the participant's condition.
All laboratory tests with values considered clinically significantly abnormal during participation 
in the study should be repeated until the values return to normal or Baseline or are no longer 
considered clinically significant by the investigator or Medical Monitor.
If such values do not return to normal/Baseline within a period of time judged reasonable by the 
investigator, the etiology should be identified, and the sponsor notified.
All protocol-required laboratory assessments, as defined in Appendix 2, Section 10.2, must be 
conducted in accordance with the laboratory manual and the Schedule of Activities.
If laboratory values from nonprotocol specified laboratory assessments performed at the 
institution’s local laboratory require a change in participant management or are considered 
clinically significant by the investigator (eg, SAE or AE or dose modification), then the results 
must be recorded in the eCRF.
8.2.5
Assessment and management of TB and TB risk factors
Precautions are being taken within this protocol to monitor the risk of TB infection in this study 
(see Section 5.2, Exclusion Criterion 9). Any presumptive diagnosis or the diagnosis of a TB 
infection is a reportable event. Assessment and management of TB and TB risk factors should 
follow local or national guidelines. 
8.2.5.1
Tuberculosis assessment
Monitoring for TB during the study
Study participants will be monitored for signs/symptoms of TB using routine pharmacovigilance 
measures for AEs. Study participants reporting AEs related to signs/symptoms of TB will be 
evaluated for LTB and active TB according to the local medical practice guidelines.
Confirmed LTB, active TB, and NTMBI must be reported to UCB immediately regardless of 
seriousness using the SAE Report Form. Additional information received by the investigator 
should be provided within 24 hours of awareness.
Once withdrawn from study treatment, study participants should return for the EW and complete 
all EOS assessments.
TB signs and symptoms questionnaire
Study participants will be evaluated both for signs and symptoms of latent or active TB infection 
and for risk factors for exposure to TB using the TB questionnaire (Appendix 19, Section 10.19 ) 
as indicated in the Schedule of Activities (Section 1.3).
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03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
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Page 90 of 220
The TB questionnaire should be completed accurately and filed as a critical source document. 
The questionnaire will assist with the identification of participants who may require therapy for 
TB.
A “Yes” response to any of the questions in the TB questionnaire during the study may trigger 
further assessments to determine if the participant has either LTB infection or active TB 
infection. As an example, a participant who answers “Yes” at Screening to the question 
 
 should not be allowed into the study 
pending further assessments per local/national guidelines. 
8.2.5.2
Tuberculosis management
In line with the World Health Organization (WHO) and the Centers for Disease Control and 
Prevention (CDC) guidelines, UCB has adopted the following definitions for latent TB, active 
TB and non-tuberculosis mycobacterium infection for the purposes of its clinical trials.
Latent TB
Latent TB infection is defined an infection by Mycobacterium tuberculosis with:
•
a positive IGRA test or 2 indeterminate IGRA tests AND
•
a chest x-ray [or other imaging]) negative for TB infection AND
•
the absence of signs, symptoms (eg, evidence of organ specific involvement, or physical 
findings) suggestive of TB infection.
Active TB and nontuberculous mycobacterium infection
A clinically verified case of TB meets the following criteria:
•
a positive Tuberculin Skin Test (TST) or positive IGRA for Mycobacterium tuberculosis
•
other signs and symptoms compatible with TB (eg, abnormal chest radiograph, abnormal
chest computerized axial tomography scan or other chest imaging study, or other clinical 
evidence of active disease)
Nontuberculous mycobacterium infection (NTMBI) is defined as a clinical infection caused by 
mycobacterial species other than those belonging to the Mycobacterium tuberculosis complex.
Study participants who develop active TB or NTMB infection during the study must be 
withdrawn from the study. The participant must be permanently discontinued from IMP and the 
EW Visit must be scheduled as soon as possible, but no later than the next scheduled visit.
Participants should be encouraged to enter the SFU period, attend Visit 28, and keep the EOS 
Visit as specified by the protocol. Treatment for active TB or NTMB should be started 
immediately based on local guidelines.
Confirmed active TB is always considered an SAE. UCB’s process requires that this must be 
captured on an SAE report form and provided to UCB in accordance with SAE reporting 
requirements. Follow-up reports should be completed as per protocol requirement until such time 
as the TB infection resolves (Appendix 3, Section 10.3).
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 91 of 220
LTB infection, active TB, or other NTMB identified during study
During TP0003, study participants who develop evidence of LTB infection, active TB, or NTMB 
infection will be referred to an appropriate TB specialist (pulmonologist or infectious disease 
specialist) for further evaluation. These study participants will not be permitted to enroll into 
TP0004. Study participants diagnosed with active TB or LTB infection should receive 
appropriate TB treatment or prophylaxis therapy. The study participant should be transferred to 
the care of their physician and managed according to the standard of care.
If infection with NTMB is identified during the study, the same procedure as for active TB 
acquired during the study and compliant TB treatment shall be followed.
Follow-up information of suspected and confirmed TB cases should be provided to UCB at least 
after 3, 9, and 12 months of the start date of anti-TB treatment, including hematological and 
biochemical safety parameters, chest x-ray evolution data, and TB diagnostic procedures used to 
follow up and confirm recovery of TB.
8.2.6
Splenectomized study participants
For Japan-specific regulations, see Appendix 8, Section 10.8.
Study participants who have previously undergone a splenectomy will be included in the study 
provided they do not meet the protocol defined exclusion criteria (Section 5.2) in order to 
optimize protection against OPSI. Adequate vaccination for all splenectomized participants 
within 4 years prior to enrollment is preferred. Splenectomized study participants should be 
vaccinated against the encapsulated organisms such as S. pneumoniae, N. meningitidis, and H. 
influenzae (as per local/or a national guidance, as applicable) as evidenced from personal 
immunization records. Study participants who are due to receive a booster, can be screened after 
they have received the required booster. However, if the next booster is due during the study, to 
avoid the treatment interruption, it can be given ahead of the 5-year schedule if needed, and prior 
to enrollment.
Splenectomized study participants without any prior vaccination against one or all of the above-
mentioned bacteria and who are willing to participate in the study, will have to undergo a 
Prolonged Screening Period after signing the ICF. During this period, splenectomized study 
participants will receive the required vaccinations against the above-mentioned bacteria (see 
Table 1-3). 
Splenectomized participants can be enrolled in the study if they have documentation of previous 
vaccination within the past 4 years for S. Pneumoniae, H. influenzae and N. meningitidis (as per 
local/national guidance) or have completed the required vaccinations during the Prolonged 
Screening Period.
Additionally, for the whole duration of the study, splenectomized participants will be required to 
carry a card indicating they have undergone splenectomy and may be at increased risk of 
infection particularly with encapsulated organisms. Splenectomized study participants should 
have a prophylactic antibiotic available or take already an antibiotic as per local guidance.
Antibody titers against S. pneumoniae, N. meningitidis, and H. influenzae in splenectomized 
study participants will be collected predose at W1 (Baseline), W3, W25 (EW Visit) and at the 
EOS Visit.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 92 of 220
Antibody titers against tetanus will be collected in all participants at Baseline (Day1), W3 
(predose), W25 (EW Visit), and EOS Visit.
8.3
Adverse events
The definitions of an AE or SAE can be found in Appendix 3, Section 10.3.
Adverse events will be reported by the study participant (or, when appropriate, by a caregiver, 
surrogate, or the participant's legally authorized representative).
The investigator and any designees are responsible for detecting, documenting, and recording 
events that meet the definition of an AE or SAE and remain responsible for following up AEs 
that are serious, considered related to the study treatment or study procedures, or that caused the 
participant to discontinue study treatment or TP0003 (see Section 7).
In order to protect the blind, the events of hypogammaglobulinemia should not be captured as an 
AE in the eCRF. 
8.3.1
Time period and frequency for collecting AE and SAE information
All SAEs and AEs will be collected from the time of signing the ICF until the EOS Visit at the 
time points specified in the Schedule of Activities (Section 1.3).
All SAEs will be recorded and reported to UCB or designee within 24 hours, as indicated in 
Appendix 3, Section 10.3. The investigator will submit any updated SAE data to UCB within 
24 hours of it being available.
The investigator is specifically requested to collect and report to UCB (or its representative) any 
SAEs (even if the investigator is certain that they are in no way associated with the IMP), up to 
30 days from the end of the study for each participant, and to also inform participants of the need 
to inform the investigator of any SAE within this period. Serious AEs that the investigator thinks 
may be associated with the IMP must be reported to UCB regardless of the time between the 
event and the end of the study.
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Appendix 3, Section 10.3.
8.3.2
Method of detecting AEs and SAEs
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.
8.3.3
Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts. All SAEs and nonserious AEs of special interest and AEs of special 
monitoring (AESM) (as defined in Sections 8.3.7 and Section 8.3.8, respectively), will be 
followed until resolution, stabilization, the investigator determines that it is no longer clinically 
significant, the event is otherwise explained, or the participant is lost to follow up (as defined in 
Section 7.3). Further information on follow-up procedures is provided in Appendix 3, 
Section 10.3.
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03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 93 of 220
8.3.4
Regulatory reporting requirements for SAEs
Prompt notification by the investigator to the sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of study participants and the safety of a 
IMP under clinical investigation are met.
UCB has a legal responsibility to notify both the local regulatory authority and other regulatory 
agencies about the safety of a IMP under clinical investigation. UCB will comply with country-
specific regulatory requirements relating to safety reporting to the regulatory authority, 
Institutional Review Board (IRB)/Independent Ethics Committee (IEC), and investigators.
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
according to local regulatory requirements and sponsor policy and forwarded to investigators as 
necessary.
An investigator who receives an investigator safety report describing a SAE or other specific 
safety information (eg, summary or listing of SAEs) from UCB will review and then file it along 
with the IB and will notify the IRB/IEC, if appropriate according to local requirements.
8.3.5
Pregnancy
Details of all pregnancies in female participants and, if indicated, female partners of male 
participants will be collected after the start of study treatment and until 3 months after dosing.
If a pregnancy is reported, the investigator must immediately inform UCB within 24 hours of 
learning of the pregnancy and should follow the procedures outlined in Appendix 4, 
Section 10.4.
The study participant must be withdrawn from the study and permanently discontinued from 
IMP as soon as the pregnancy is known (by positive pregnancy test), and the following should be 
completed:
•
The study participant should return for the EW visit and complete the SFU Period.
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, or ectopic pregnancy) are considered SAEs.
In case of confirmed pregnancy in TP0003, the study participant cannot enroll into TP0004.
8.3.6
Anticipated serious adverse events
The following anticipated SAEs are anticipated to occur in the population studied in this protocol 
at some frequency that is independent of drug exposure (Table 8-1).
This list does not change the investigator’s obligation to report all SAEs (including anticipated 
SAEs) as detailed in Section 8.3.1 and Appendix 3, Section 10.3.
Table 8-1:
Anticipated serious adverse events for ITP population
Anemia
Hemorrhagic events
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03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 94 of 220
8.3.7
Adverse events of special interest
An AE of special interest is any AE that a regulatory authority has mandated be reported on an 
expedited basis, regardless of the seriousness, expectedness, or relatedness of the AE to the 
administration of a UCB product/compound. 
Potential Hy’s Law, defined as ≥3xULN ALT or AST with coexisting ≥2xULN total bilirubin in 
the absence of ≥2xULN ALP, with no alternative explanation for the biochemical abnormality, 
must ALWAYS be reported to UCB as an AE of special interest (ie, without waiting for any 
additional etiologic investigations to have been concluded). Follow-up information should then 
be reported if an alternative etiology is identified during investigation and monitoring of the 
participant.
See Appendix 6, Section 10.6 for further information on liver safety monitoring.
8.3.8
Adverse events of special monitoring
For rozanolixizumab, AESM that require immediate reporting (within 24 hours regardless of 
seriousness) to UCB are:
•
Severe headache
•
Severe GI disorders (ie, diarrhea, abdominal pain, vomiting)
•
Opportunistic infection
•
Arterial and venous thrombotic and thromboembolic events
An AESM is not necessarily a serious adverse event unless one of the seriousness criteria 
defined in the Appendix 3 (Section 10.3) is met. All AESM will follow the SAE recording and 
reporting procedures as indicated in Appendix 3, Section 10.3.
In case of severe headache or serious headache (regardless of severity), the headache 
questionnaire (Appendix 20, Section 10.20) must be completed. The questionnaire should also be 
completed in case of moderate headache although moderate headache is not considered an 
AESM. Additional procedures for management of headaches are provided in Appendix 22, 
Section 10.22.
Procedures for the management of diarrhea are provided in Appendix 23, Section 10.23.
Although hypersensitivity reactions including infusion-related reactions and anaphylaxis are not 
classified as AESM, these AEs will be monitored by the investigators. If such an event is 
suspected it should be managed according the guidance provided in Appendix 24, Section 10.24.
In case of suspected anaphylaxis, the Sampson’s Criteria (Sampson et al, 2006) (Appendix 21, 
Section 10.21) should be completed. All hypersensitivity reactions will be recorded and reported 
as per the AE reporting procedure outlined in Appendix 3, Section 10.3.
8.3.9
Treatment-emergent adverse events
Treatment-emergent AEs are defined as AEs starting after the time of first IMP administration up 
to and including 8 weeks after the final dose.
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03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 95 of 220
8.3.10
COVID-19 vaccination
Coronavirus disease 2019 vaccines will be recorded on the concomitant medication eCRF page 
(Section 6.4.1). If an AE is considered related to COVID-19 vaccine, causality assessment 
should be entered on the AE eCRF (in the AE eCRF page, there is the possibility to assess 
causality to the IMP or to any concomitant medication). Note that in this case, the national
recommendation for reporting an AE related to COVID-19 vaccines should be followed. If an 
AE is the result of an interaction of a COVID-19 vaccine with the IMP in the clinical study then 
the causal association should be for both IMP and COVID-19 vaccine. In case of a seriousness 
criteria, the Suspected Unexpected Serious Adverse Reaction process will be followed.
8.4
Safety signal detection
Selected data from this study will be reviewed periodically to detect as early as possible any 
safety concern(s) related to the IMP so that investigators, clinical study participants, regulatory 
authorities, and IRBs/IECs will be informed appropriately and as early as possible.
In addition, an unblinded IDMC will periodically review and monitor safety data from this study 
and advise UCB. Details are provided in the IDMC Charter.
The Study Physician or medically qualified designee/equivalent will conduct an ongoing review 
of SAEs and perform ongoing SAE reconciliations in collaboration with the PS representative.
As appropriate for the stage of development and accumulated experience with the IMP, 
medically qualified personnel at UCB may identify additional safety measures (eg, AEs, vital 
signs, laboratory, or ECG results) for which data will be periodically reviewed during the course 
of the study.
8.5
Treatment of overdose
For this study, any dose increase of 10% or greater than the assigned dose for each administered 
dose of IMP will be considered an overdose, irrespective of the weight tier band. Overdose 
events are only considered AEs or SAEs if there are associated clinical signs and symptoms or if 
the act of taking the excess IMP itself is an AE or SAE (eg, suicide attempt).
UCB does not recommend specific treatment for an overdose.
In the event of an overdose, the investigator or treating physician should:
1. Contact the Medical Monitor immediately.
2. Closely monitor the participant for any AE/SAE and laboratory abnormalities for at least
5 days. 
3. Obtain a plasma sample for PK analysis within 3 days from the date of the final dose of study 
treatment if requested by the Medical Monitor (determined on a case-by-case basis).
4. Document the quantity of the excess dose as well as the duration of the overdose in the 
eCRF.
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the Medical Monitor based on the clinical evaluation of the participant.
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03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 96 of 220
8.6
Pharmacokinetics and antidrug antibodies
Whole blood samples will be collected for measurement of plasma concentrations of 
rozanolixizumab and ADA as specified in the Schedule of Activities (Section 1.3). Blood 
samples may be collected at additional time points during the study if warranted and agreed upon 
between the investigator and the sponsor. Instructions for the collection and handling of 
biological samples will be provided in the laboratory manual for this study. The actual date and 
time (24-hour clock time) of each sample will be recorded.
Samples will be used to evaluate the PK of rozanolixizumab and ADA and may be used for 
establishing assay parameters (eg, ADA cut point setting and PK selectivity assessment). 
Samples collected for analyses of rozanolixizumab concentration may also be used to evaluate 
safety or efficacy aspects related to concerns arising during or after the study.
Participant confidentiality will be maintained. At visits during which only plasma samples for the 
determination of concentration of rozanolixizumab will be taken, 1 sample of sufficient volume 
can be used.
Drug concentration information that may unblind the study will not be reported to study sites or 
blinded personnel until the study has been unblinded.
Any changes in the timing or addition of time points for any planned study assessments must be 
documented and approved by the relevant study team member and then archived in the UCB and 
site study files but will not constitute a protocol amendment. The IRB/IEC will be informed of 
any safety issues that require alteration of the safety monitoring scheme or amendment of the 
ICF.
8.7
Pharmacodynamics
Venous blood samples will be collected at time points specified in the Schedule of Activities 
(Section 1.3) for measurement of:
•
Serum IgG and IgG subclasses concentrations
•
Serum IgA, IgE, and IgM concentrations
•
Serum ITP-specific autoantibodies
For all PD assessments, blood samples will be collected predose at the Baseline Visit (Day 1). 
Instructions pertaining to sample collection, processing, storage, labeling, and shipping are 
provided in the laboratory manual for this study. Results of the ITP-specific autoantibodies 
analyses will not be outlined in the Clinical Study Report for this study.
8.8
Genetics
8.8.1
Pharmacogenomics
Blood sample for DNA and RNA biomarkers will be collected as specified in the Schedule of 
Activities (Section 1.3) from study participants who have consented to participate in the 
pharmacogenomics sub-study. This sampling is optional for study participants and requires a 
separate informed consent. A decision not to consent does not exclude the study participant from 
the study. 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 97 of 220
If not used immediately, these samples will be stored at -80°C for up to 20 years for later 
exploratory analyses. Any exploratory biomarker or genomic analysis will only ever be related to 
the exploration of the cause, progression, and appropriate treatment of ITP.
The nature and format of these tentative additional analyses will be determined at a later time. 
Details on the collection, storage, preparation, and shipping of samples will be presented in the 
laboratory manual provided separately. Instructions pertaining to sample collection, processing, 
storage, labeling, and shipping are provided in the laboratory manual for this study. Detailed 
information on sample analyses will be provided in a bioanalytical report. Results of the DNA 
and RNA biomarker analyses will not be outlined in the Clinical Study Report for this study. 
8.8.2
Immunology
Blood samples for immunological testing are required and will be collected from all study 
participants in this study predose, as specified in the Schedule of Activities (Section 1.3) for 
measurement of:
•
Serum complements (C3, C4)
•
Plasma complements (C3a, C5a)
Serum complements (C3, C4) and plasma complements (C3a, C5a) should be taken predose at 
Baseline (Day 1) and at Week 25 for all study participants. In participants who experience an 
infusion reaction or hypersensitivity reaction at the site, samples should also be taken 2 hours 
postevent and 4 hours postevent or otherwise as soon as possible but prior to the next dosing, as 
specified in the Schedule of Activities (Section 1.3).
Instructions pertaining to sample collection, processing, storage, labeling, and shipping are 
provided in the laboratory manual for this study.
8.9
Exploratory biomarkers
Collection of samples for exploratory biomarker research is also part of this study. 
Blood samples for biomarker research are required and will be collected from all study 
participants in this study. Exploratory biomarker samples should be taken predose at Baseline 
(Day 1) and Week 25 for all study participants. In study participants who experience severe 
and/or serious headaches or severe and/or serious GI disorders (ie, abdominal pain, diarrhea, 
vomiting), samples should also be taken 4 hours postevent, or otherwise as soon as possible but 
prior to the next dosing, as specified in the Schedule of Activities (Section 1.3).
Protein and metabolites biomarkers such as but not limited to albumin, B-cell activating factor, 
and Circulating Immune Complexes may be measured to assess the effect of rozanolixizumab on 
exploratory biomarkers, and explore the relationship between protein, and metabolite biomarkers 
and cause, progression, and appropriate treatment of ITP.
If not used immediately, these samples will be stored at -80°C for up to 20 years for later 
exploratory analyses. Any exploratory biomarker will only ever be related to the exploration of 
cause, progression, and appropriate treatment of ITP. They may also be used to develop 
tests/assays including diagnostic tests related to rozanolixizumab and/or FcRn inhibitor and ITP.
The nature and format of these tentative additional analyses will be determined at a later time. 
Details on the collection, storage, preparation, and shipping of samples will be presented in the 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 98 of 220
laboratory manual provided separately. Detailed information on sample analyses will be 
provided in a bioanalytical report.
8.10
Medical resource utilization and health economics
Medical Resource Utilization and Health Economics parameters are not evaluated in this study.
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof. 


UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 99 of 220
9
STATISTICAL CONSIDERATIONS
A description of statistical methods follows and will be described in more detail in the SAP.
9.1
Definition of analysis sets
•
Enrolled Set: All study participants who have signed the informed consent.
•
Randomized Set (RS): All enrolled study participants who were randomized. This is 
equivalent to the Intent-to-Treat Set.
•
Safety Set (SS): All randomized study participants who received at least one dose of IMP 
(partial or full). Analysis of this set will be according to the treatment the participants 
actually received and will be used for the demographic and safety analyses.
The analysis of the PD (excluding total IgG, and IgG subclasses) and immunologic variables 
will be performed on the SS. Selected outputs may be repeated for the PD Per-Protocol Set 
(PD-PPS). Further details will be provided in the SAP.
•
Full Analysis Set (FAS): Consists of all study participants randomized who have received at 
least one complete sc infusion of IMP, have a valid Baseline, and at least 1 valid 
post-Baseline platelet count measurement during Weeks 13-25.
•
Pharmacodynamic Per-Protocol Set (PD-PPS): A subset of the SS, consisting of those study 
participants who had no important protocol deviations potentially affecting the serum 
concentration of total IgG, as confirmed during a pre-analysis review of the data prior to 
database lock. Protocol deviations may not necessarily lead to total exclusion of a participant 
from the PD-PPS but may lead to exclusion of specific data.
•
Pharmacokinetic Per-Protocol Set (PK-PPS): A subset of the SS, consisting of those study 
participants who received at least 1 dose, had at least 1 valid PK measurement, and no 
important protocol deviations affecting the PK variable, as confirmed during a pre-analysis 
review of the data prior to database lock.
The RS will be the primary analysis set for efficacy analyses.
The PD-PPS will be used for the analysis of the total IgG, and IgG subclasses.
9.2
General statistical considerations
All analyses will be performed using SAS® version 9.2 or later (SAS Institute, Cary, NC, USA). 
Continuous variables will be summarized by visit (where applicable) with the statistics including 
the number of participants (n), mean, standard deviation (SD), median, minimum, and maximum.
Data listings containing all documented data and all calculated data will be generated.
Baseline will be the last non-missing data collected prior to the dose of IMP, and measurement-
specific Baseline values will be defined in the SAP.
Data handling conventions for data affected by COVID-19 will be detailed fully in the SAP.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 100 of 220
9.3
Planned efficacy/outcome analyses
9.3.1
Analysis of the primary efficacy/primary endpoint
The primary efficacy variable is the durable clinically meaningful platelet response ≥50×109/L, 
for at least 8 out of 12 weeks during the last 12 weeks (platelet count recorded at Week 14 to 
Week 25 corresponding to the response achieved following dosing at Week 13 to Week 24). 
Missing platelet count at any visit will be considered "worst case" and set to zero ("no platelet 
response") for that specific visit.
The primary and supportive analyses for the durable platelet count endpoint are detailed in 
Table 9-1. The main intercurrent events are rescue therapy prior to Week 25 and treatment 
discontinuation (withdrawal from study) due to TEAEs. 
Confirmatory testing of single hypotheses is based on a closed-testing procedure.
The primary analysis of the study will use a Stratified Cochran-Mantel-Haenszel test statistic.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 101 of 220
Table 9-1:
Estimands for the primary endpoint
Estimand
Objective 
Clinical 
Category
Statistical 
Category
Variable/ 
Endpoint
Population
IESa
PLSb (Analysis)
Primary Objective: To demonstrate clinical efficacy of rozanolixizumab as a maintenance treatment in participants with primary ITP
Platelet 
Count
Primary/MCP
Durable Clinically 
Meaningful 
Platelet Response 
of ≥50×109/L, for 
at least 8 out of 12 
weeks during the 
last 12 weeks 
(Week 13 to 
Week 25)
RS who 
were 
randomized 
to 
rozanolixiz
umab 
weekly 
dosing 
compared 
against 
those who 
received 
placebo.
A composite strategy will be used, 
in which participants who require 
rescue therapy, who experience 
any TEAEs leading to treatment 
discontinuation, discontinue prior 
to receiving IMP, or do not have a 
post-treatment assessment will be 
considered as nonresponders.
To test of the null hypothesis (H0) 
in participants who have achieved a 
durable platelet count that the true 
common odds ratio between 
treatment arms is 1 (odds ratio = 1) 
vs the alternative hypothesis (Ha) 
that the odds ratio is less than 1, a 
Cochran-Mantel-Haenszel model 
adjusted for the stratification 
factors, namely baseline degree of 
thrombocytopenia (platelet count 
< or ≥15×109/L), history of 
splenectomy (yes or no).
Platelet 
Count
Sensitivity
Durable Clinically 
Meaningful 
Platelet Response 
of ≥50×109/L, for 
at least 8 out of 12 
weeks during the 
last 12 weeks 
(Week 13 to 
Week 25)
RS who 
were 
randomized 
to 
rozanolixiz
umab 
weekly 
dosing 
compared 
against 
those who 
received 
placebo.
A composite strategy: participants 
who experience any TEAEs 
leading to treatment 
discontinuation will be considered 
as nonresponders.
All other cases included but not 
limited to participants who 
discontinue prior to receiving 
IMP, or do not have a 
post-treatment assessment or 
participants who require rescue 
therapy the response variable will 
be imputed using a fully 
conditional specification method.
To test of the null hypothesis (H0) 
in participants who have achieved a 
durable platelet count that the true 
common odds ratio between 
treatment arms is 1 (odds ratio = 1) 
vs the alternative hypothesis (Ha) 
that the odds ratio is less than 1, a 
Cochran-Mantel-Haenszel model 
adjusted for the stratification 
factors, namely baseline degree of 
thrombocytopenia (platelet count 
< or ≥15×109/L), history of 
splenectomy (yes or no).
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 102 of 220
Estimand
Objective 
Clinical 
Category
Statistical 
Category
Variable/ 
Endpoint
Population
IESa
PLSb (Analysis)
Platelet 
Count
Supplemental
Durable Clinically 
Meaningful 
Platelet Response 
of ≥50×109/L, for 
at least 8 out of 12 
weeks during the 
last 12 weeks 
(Week 13 to 
Week 25)
RS who 
were 
randomized 
to 
rozanolixiz
umab 
weekly 
dosing 
compared 
against 
those who 
received 
placebo.
A composite strategy, in which 
participants who require rescue 
therapy, who experience any 
TEAEs leading to treatment 
discontinuation, discontinue prior 
to receiving IMP, or do not have a 
post-treatment assessment will be 
considered as nonresponders.
Difference in proportions of 
participants between treatment 
arms who achieved a durable 
platelet count, analyzed using 
Fisher’s Exact Test. 
Platelet 
Count
Sensitivity
Durable Clinically 
Meaningful 
Platelet Response 
of ≥50×109/L, for 
at least 8 out of 12 
weeks during the 
last 12 weeks 
(Week 13 to Week 
25)
FAS who 
were 
randomized 
to 
rozanolixiz
umab 
weekly 
dosing 
compared 
against 
those who 
received 
placebo
Composite strategy as described 
above with the addition of 
excluding participants who have 
not received a sufficient sc 
infusion. Participants who are not 
part of the FAS population will 
not be included in the analysis.
To test of the null hypothesis (H0) 
in participants who have achieved a 
durable platelet count of ≥50×109/L 
for at least 8 weeks out of the last 
12 weeks (Week 13 to Week 25) 
that the true common odds ratio 
between treatment arms is 1 (odds 
ratio = 1) vs the alternative 
hypothesis (Ha) that the odds ratio 
is less than 1, a logistic regression 
model adjusted for the stratification 
factors, namely baseline degree of 
thrombocytopenia (platelet count 
< or ≥15×109/L), history of 
splenectomy (yes or no).
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 103 of 220
Estimand
Objective 
Clinical 
Category
Statistical 
Category
Variable/ 
Endpoint
Population
IESa
PLSb (Analysis)
Platelet 
Count
Sensitivity
Durable Clinically 
Meaningful 
Platelet Response 
of ≥50×109/L, for 
at least 8 out of 12 
weeks during the 
last 12 weeks 
(Week 13 to 
Week 25)
RS who 
were 
randomized 
to 
rozanolixiz
umab 
weekly 
dosing 
compared 
against 
those who 
received 
placebo
Composite strategy as described 
for the primary analysis.
To test of the null hypothesis (H0) 
in participants who have achieved a 
durable clinically meaningful 
platelet response of ≥50×109/L for 
at least 8 out of 12 weeks during 
the last 12 weeks (Week 13 to 
Week 25) that the true common 
odds ratio between treatment arms 
is 1 (odds ratio = 1) vs the 
alternative hypothesis (Ha) that the 
odds ratio is less than 1, a logistic 
regression model adjusted for the 
stratification factors, namely 
baseline degree of 
thrombocytopenia (platelet count 
< or ≥15×109/L), history of 
splenectomy (yes or no).
H0=null hypothesis; Ha=alternative hypothesis; IES=Intercurrent event(s) strategy; IMP=investigational medicinal product; FAS=Full 
Analysis Set; MCP=Multiple comparisons procedure; FWER=family-wise error-rate; PLS=Population-level summary; RS=Randomized 
Set; TEAE=treatment-emergent adverse event
MCP: FWER controlled for hypothesis testing of selected endpoints as specified.
a The potential impact of any temporary treatment discontinuations (as detailed in Section 7.1.4) on the estimand strategy will be explored 
and detailed in the Statistical Analysis Plan.
bAll estimand attributes explicitly identified for primary/secondary and selected key estimands only.
PUBLIC COPY 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 104 of 220
9.3.2
Analysis of the secondary efficacy endpoints
The analyses for secondary endpoints are detailed in Table 9-2. The main intercurrent events are 
the use of rescue therapy prior to Week 25 and treatment discontinuation (or withdrawal from 
study) due to treatment emergent AEs.
In addition, all continuous secondary efficacy variables will be listed and summarized 
descriptively by treatment group and week. Descriptive statistics will be generated for the 
observed values and the change from Baseline. For the binary variables, frequency counts and 
percentages will be produced.
A sequential hierarchical test procedure will be applied to protect the overall significance level 
for the multiplicity of endpoints. The predefined order of formal hypotheses testing for the 
secondary endpoints will be performed in the following sequence:
•
Cumulative number of weeks with Clinically Meaningful Platelet Response of ≥50×109/L
over the 24-week treatment period 
•
Time to first Clinically Meaningful Platelet Response of ≥50×109/L: time from starting 
treatment to achievement of first response of ≥50×109/L 
•
Clinically Meaningful Platelet Response of ≥50×109/L by Day 8
•
Response defined as platelet count ≥30×109/L and at least a 2-fold increase of the 
Baseline count confirmed on at least 2 separate occasions at two adjacent nominal visits 
at least 7 days apart, and absence of bleeding by visit
•
Time to first rescue therapy
•
Change from Baseline to Week 25 in ITP-PAQ Symptoms Score
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 105 of 220
Table 9-2:
Estimands for secondary endpoints
Estimand
Objective 
Clinical 
Category
Statistical 
Category
Variable/Endpoint
Population
IESa
PLSb (Analysis)
Secondary Objective: To assess the safety and tolerability of rozanolixizumab
Platelet 
Count
Secondary/
MCP
Cumulative number 
of weeks with 
Clinically 
Meaningful Platelet 
Response of 
≥50×109/L over the 
24-week treatment 
period
RS who 
were 
randomized 
to 
rozanolixiz
umab 
weekly 
dosing 
compared 
against 
those who 
received 
placebo.
A composite endpoint will be 
used where, in the case rescue 
therapy are taken, only the 
platelet data up to the start date 
of rescue therapy will be 
utilized for the statistical 
analysis. Participants who take 
rescue therapy or who are 
withdrawn owing to TEAEs 
are defined as having a loss of 
durable platelet response at the 
time of the event occurring.
Cumulative number of 
weeks with clinically 
meaningful platelet 
response will be analyzed 
using an analysis of 
covariance with fixed terms 
for treatment, splenectomy, 
degree of thrombocytopenia 
(platelet count < or 
≥15×109/L). Estimated 
means and 95% CI will be 
presented for each treatment 
group.
Platelet 
Count
Secondary/
MCP
Time to first 
Clinically 
Meaningful Platelet 
Response of 
≥50×109/L: time 
from starting 
treatment to 
achievement of first 
response of 
≥50×109/L 
RS who 
were 
randomized 
to 
rozanolixiz
umab 
weekly 
dosing 
compared 
against 
those who 
received 
placebo.
A composite strategy will be 
used where, in the case rescue 
therapy are taken, only the 
platelet data up to the start date 
of rescue therapy will be 
utilized for the statistical 
analysis. Participants who take 
rescue therapy or who are 
withdrawn due to TEAEs are 
defined as having a loss of 
clinically meaningful platelet 
response and will be censored 
at the time of the event.
Time to first Clinically 
Meaningful Response will 
be analyzed using a 
stratified Log Rank Test 
with fixed terms for 
treatment, splenectomy, 
degree of thrombocytopenia 
(platelet count < or ≥ 
15×109/L). 
Estimated hazard ratios and 
95% CIs will be presented. 
The time to first Clinically 
Meaningful Response will 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 106 of 220
Estimand
Objective 
Clinical 
Category
Statistical 
Category
Variable/Endpoint
Population
IESa
PLSb (Analysis)
be presented graphically 
using a Kaplan-Meier curve.
Platelet 
Count
Secondary/
MCP
Clinically 
Meaningful 
Response by Day 8, 
defined as: platelet 
count ≥50×109/L
RS who 
were 
randomized 
to 
rozanolixiz
umab 
weekly 
dosing 
compared 
against 
those who 
received 
placebo
A composite strategy will be 
used for rescue therapy, ie, 
participants who require rescue 
therapy will be considered a 
non-responder. The same 
strategy will be used for 
TEAEs leading to treatment 
discontinuation, and 
participants who discontinue 
prior to receiving IMP, do not 
have a valid Baseline 
assessment or do not have a 
post-treatment assessment.
To test of the null 
hypothesis (H0) in 
participants who have 
achieved a Clinically 
Meaningful Response by 
Day 8, defined as: Platelet 
count ≥50×109/L that the 
true common odds ratio 
between treatment arms is 1 
(odds ratio = 1) vs the 
alternative hypothesis (Ha) 
that the odds ratio is less 
than 1, a Cochran-Mantel 
Haenszel model adjusted for 
the stratification factors, 
namely baseline degree of 
thrombocytopenia (platelet 
count < or ≥15×109/L), 
history of splenectomy (yes 
or no).
Platelet 
Count
Secondary/
MCP
Response defined 
as platelet count 
≥30×109/L and at 
least a 2-fold 
increase of the
Baseline count 
confirmed on at 
least 2 separate 
RS who 
were 
randomized 
to 
rozanolixiz
umab 
weekly 
dosing 
A composite strategy as 
described for Clinically 
Meaningful Response by 
Day 8 will be used.
To test of the null 
hypothesis (H0) in 
participants who have 
achieved a Response by 
Day 8, defined as: Platelet 
count ≥30×109/L and at 
least a 2-fold increase of the 
Baseline count, confirmed 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 107 of 220
Estimand
Objective 
Clinical 
Category
Statistical 
Category
Variable/Endpoint
Population
IESa
PLSb (Analysis)
occasions at two 
adjacent nominal 
visits at least 7 days 
apart, and absence 
of bleeding.
compared 
against 
those who 
received 
placebo
on at least 2 separate 
occasions at two nominal 
visits at least 7 days apart, 
and absence of bleeding, 
that the true common odds 
ratio between treatment 
arms is 1 (odds ratio = 1) vs 
the alternative hypothesis 
(Ha) that the odds ratio is 
less than 1, a 
Cochran-Mantel Haenszel 
model adjusted for the 
stratification factors, namely 
baseline degree of 
thrombocytopenia (platelet 
count < or ≥15×109/L), 
history of splenectomy (yes 
or no).
Platelet
Count
Sensitivity
Response defined 
as platelet count 
≥30×109/L and at 
least a 2-fold 
increase of the 
Baseline count 
confirmed on at 
least 2 separate 
occasions at two 
adjacent nominal 
visits at least 7 days 
apart, and absence 
of bleeding.
RS who 
were 
randomized 
to 
rozanolixiz
umab 
weekly 
dosing 
compared 
against 
those who 
received 
placebo
A composite strategy as 
described for Clinically 
Meaningful Response by 
Day 8 will be used.
Difference in the proportion 
of participants between 
treatment arms who have 
achieved a durable platelet 
count analyzed using 
logistic regression model 
adjusting for the covariates 
treatment, splenectomy, and 
degree of thrombocytopenia 
(platelet count < or 
≥15×109/L).
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 108 of 220
Estimand
Objective 
Clinical 
Category
Statistical 
Category
Variable/Endpoint
Population
IESa
PLSb (Analysis)
Rescue 
therapy
Secondary
Time to first rescue 
therapy. 
RS who 
were
randomized 
to 
rozanolixiz
umab 
weekly 
dosing 
compared 
against 
those who 
received 
placebo.
A composite strategy will be 
used where, in the case rescue 
therapy are taken, only the 
platelet data up to the start date 
of rescue therapy will be 
utilized for the statistical 
analysis. Participants who take 
rescue therapy or who are 
withdrawn due to TEAEs are 
defined as having a loss of 
clinically meaningful platelet 
response and will be censored 
at the time of the event. 
Time to first rescue therapy 
use will be analyzed using a 
stratified Log Rank Test 
model with fixed terms for 
treatment, splenectomy, 
degree of thrombocytopenia 
(platelet count < or ≥ 
15×109/L). Estimated 
hazard ratios and 95% CIs 
will be presented. The time 
to first rescue therapy use 
will be presented 
graphically using a Kaplan-
Meier curve.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 109 of 220
Estimand
Objective 
Clinical 
Category
Statistical 
Category
Variable/Endpoint
Population
IESa
PLSb (Analysis)
PRO
Secondary/
MCP
Change from 
Baseline to 
Week 25 in 
ITP-PAQ Symptom 
score.
RS who 
were 
randomized 
to 
rozanolixiz
umab 
weekly 
dosing 
compared 
against 
those who 
received 
placebo.
A hypothetical strategy will be 
used for rescue therapy intake: 
ITP-PAQ Symptom scores 
after rescue medication will 
not be included in the 
estimation of the repeated 
measurement mixed model.
Change in ITP-PAQ from 
Baseline to Week 25 will be 
estimated from a 
generalized linear model 
including treatment and visit 
will be included in the 
model, adjusting for the 
covariates splenectomy, 
degree of thrombocytopenia 
(platelet count < or 
≥15×109/L) and Baseline 
ITP-PAQ Symptoms score. 
The difference between 
treatment arms will be 
compared using model-
based estimates of mean 
ITP-PAQ Symptom score in 
each arm at Week 25.
CI=confidence interval; H0=null hypothesis; Ha=alternative hypothesis; IES=Intercurrent event(s) strategy; IMP=investigational 
medicinal product; ITP-PAQ=primary Immune Thrombocytopenia Patient Assessment Questionnaire; FWER=family-wise error-rate; 
MCP=Multiple comparisons procedure; PLS=Population-level summary; PRO=patient reported outcome; RS=Randomized Set; 
TEAE=treatment emergent adverse event
MCP: FWER controlled for hypothesis testing of selected endpoints as specified (to be determined).
a The potential impact of any temporary treatment discontinuations (as detailed in Section 7.1.4) on the estimand strategy will be explored 
and detailed in the Statistical Analysis Plan.
bAll estimand attributes explicitly identified for primary/secondary and selected key estimands only.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 110 of 220
9.3.3
Other efficacy/other outcome analyses
9.3.3.1
Analysis of pharmacokinetic endpoint
The PK-PPS dataset will be used. Rozanolixizumab plasma concentration data will be listed by 
study participant and actual time. A statistical summary of rozanolixizumab plasma 
concentrations will be reported by scheduled time point overall and by body weight tier, 
stratified by dose regimen. Further details on summaries for dose modifications will be provided 
in the corresponding SAP. Summaries by geographical region may be performed. The number of 
available observations, mean, median, SD, minimum, maximum, geometric mean (and 
associated 95% CI), and geometric coefficient of variation (assuming log normally distributed 
data) will be calculated. Values below the LLOQ will be reported as LLOQ/2 for calculation of 
descriptive statistics. Descriptive statistics of concentrations will be calculated if at least two-
thirds of the individual data points are quantifiable (≥LLOQ).
Individual concentrations of rozanolixizumab may also be displayed graphically as spaghetti 
plots stratified by body weight tier (ie, changing color of line and type of data points when dose 
regimen changes, if down-titration was performed). Summaries by geographical region may be 
performed. Similarly individual plots will be performed where the potential change in dose will 
be display graphically and ADA, PK, PD and/or platelets will be evaluated and displayed. 
Further details will be provided in the SAP.
If data merit, PK data may be included in a population PK analysis, further details would be 
provided in a separate Data Analysis Plan and reported separately.
9.3.3.2
Antidrug antibodies analyses
A tiered ADA approach will be used for the study. Samples will first be evaluated in the 
screening assay using a false positivity rate of 5% (reported as negative screen or positive 
screen), followed by analysis of screened positive samples in the confirmatory assay (which is a 
drug depletion assay) to confirm the true positivity of the samples (reported as negative 
immunodepletion or positive immunodepletion). Samples that are confirmed as positive will be 
evaluated in a titration assay to quantify the ADA level and will be reported as titer (reciprocal 
dilution factor including MRD). For anti-rozanolixizumab antibody positive samples (or subset 
of), further characterization for neutralizing ADA potential in vitro will be performed, and 
results will be presented in a listing. Full details will be covered in the SAP.
The impact of ADA on PK, PD, and safety will be evaluated.
Further details will be provided in the SAP.
9.3.3.3
Analysis of pharmacodynamic endpoints
For total IgG, the absolute serum IgG and change from Baseline on serum IgG with time will be 
summarized by dose regimen in the Adaptation Period and the Maintenance Period.
Spaghetti plots of the % change from Baseline and absolute IgG levels will be displayed, 
stratification by body weight tiers may be done, as well as by dose regimen during the 
Adaptation and Maintenance Dose Period (ie, changing color of lines in graph by dose regimen 
administered). 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 111 of 220
If data merits, IgG data will be included in a population pharmacokinetic/pharmacodynamic 
analysis and link to the platelet outcome, further details would be provided in a separate data 
analysis plan (DAP) and reported separately.
9.4
Planned safety and other analyses
9.4.1
Safety analyses
The frequency and severity of all TEAEs will be presented for each treatment group separately 
by system organ class, high level term, and preferred term (Medical Dictionary for Regulatory 
Activities). Data will be further presented by randomized dosing regimen. The data will be 
displayed as number of participants experiencing the TEAE, percentage of participants, and 
number of TEAEs.
Laboratory evaluations and vital signs as well as ECG data will be analyzed over time. All safety 
analyses will be based on the SS, consisting of all participants who receive at least 1 dose of 
IMP.
9.5
Handling of protocol deviations
Important protocol deviations are identified as part of the data cleaning process in the Data 
Cleaning Plan (DCP). Ongoing data cleaning meetings will be held throughout the duration of 
the study. Objectives of these meetings include the review of important protocol deviations and 
update (if necessary) the important protocol deviation specification and discuss exclusion of 
participants from analysis populations. Furthermore, overall trends in protocol deviations will be 
discussed at the Data Evaluation Meetings. Through this ongoing data cleaning and evaluation 
process, all decisions regarding important protocol deviations and exclusions from analysis 
populations are made on an ongoing basis.
9.6
Handling of dropouts or missing data
All imputation of missing or partial dates for safety assessments, as well as handling missing 
efficacy data (where applicable), will be detailed in the SAP.
If individual platelet visit data is missing it will be set to zero; participants who are lost to 
follow-up will be imputed as nonresponders.
It is not anticipated that there will be missing data, due to the adoption of the responder endpoint 
definition, where study participants who have not met the threshold for clinically meaningful 
response will be imputed as nonresponders for the analysis.
9.7
Data monitoring
An external IDMC will be established to review the safety data at predefined intervals and ad 
hoc as needed, should emerging safety concerns arise during the study. The IDMC will have the 
possibility to unblind the data. Details of the IDMC composition, processes, and responsibilities 
will be documented in the IDMC charter. One IDMC is planned for both pivotal studies (TP0003 
and TP0006), where the safety data will be initially presented unpooled, ie, data from each study 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 112 of 220
will be reviewed separately. Key safety data may be pooled at the discretion of the IDMC for 
protection of all study participants if warranted.
The IDMC will consist of members independent from UCB. Study enrollment will not be halted 
during planned IDMC review of the safety and efficacy data. 
9.7.1
Early stopping for efficacy
Not applicable.
9.7.2
Early stopping for futility
Not applicable.
9.8
Determination of sample size
The observed response rates from Kuter et al (2008) in splenectomized participants were 38% 
(16/42) on active and 0% (0/21) on placebo. In non-splenectomized participants the rates were 
61% (25/41) and 5% (1/21), respectively.
Using the true response rate of 0.45 versus 0.05, a sample size of 60 participants randomized in a 
2:1 ratio (ie, n=40 on rozanolixizumab and n=20 on placebo) receiving weekly infusions will 
provide >90% power to detect a statistically significant difference between treatment groups 
using Fisher’s Exact Test at an alpha level of 0.025 (1-sided). By definition participants who 
dropout of the study are determined as nonresponders and are incorporated in the overall 
response rate. If the number of dropouts is greater than anticipated by 10%, the impact on the 
rozanalixizumab response rate would mean that it would drop to a response rate of 0.4. In such 
cases, the study would still achieve >80% power if the overall response rate on placebo remains 
at 0.05.
If the response rate on placebo was 0.1 rather than the anticipated 0.05, the rozanolixizumab rate 
would need to be >0.45 to achieve 80% and >0.5 to achieve 90% power. Table 9-3 provides 
power estimates for a fixed study design of n=60 participants in a 2:1 randomization ratio.
Table 9-3: Expected sample size for TP0003
Scenario
Placebo Response Rate of 0.05
Placebo Response Rate of 0.10
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 113 of 220
The power of the study maybe increased by including the platelet count data from the 
participants who received bi-weekly placebo infusions in the assessment of the rozanolixizumab 
treatment effect. For instance, if 10 participants received bi-weekly infusions on the placebo arm, 
the overall sample size would increase to n=70 (ie, n=40 on rozanolixizumab and n=30 on 
placebo), and 90% power would be achieved for rozanolixizumab response rates of >0.35 and 
>0.45 if the true placebo response rate was 0.05 and 0.10 respectively.
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof. 


UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 114 of 220
10
SUPPORTING DOCUMENTATION AND OPERATIONAL
CONSIDERATIONS
10.1
Appendix 1: Regulatory, ethical, and study oversight 
considerations
10.1.1
Regulatory and ethical considerations
The study will be conducted under the auspices of an IRB/IEC, as defined in local regulations, 
International Council for Harmonisation-Good Clinical Practice (ICH-GCP), and in accordance 
with the ethical principles that have their origin in the Declaration of Helsinki.
The investigator/UCB will ensure that an appropriately constituted IRB/IEC that complies with 
the requirements of the current ICH-GCP version or applicable country-specific regulations will 
be responsible for the initial and continuing review and approval of the clinical study. Prior to 
initiation of the study, the investigator/UCB will forward copies of the protocol, ICF, IB, 
investigator’s curriculum vitae (if applicable), advertisement (if applicable), and all other 
participant-related documents to be used for the study to the IRB/IEC for its review and 
approval.
Before initiating a study, the investigator will have written and dated full approval from the 
responsible IRB/IEC for the protocol.
The investigator will also promptly report to the IRB/IEC all changes in the study, all 
unanticipated problems involving risks to participants or others, and any protocol deviations, to 
eliminate immediate hazards to participants.
The investigator will not make any changes in the study or study conduct without IRB/IEC 
approval, except where necessary to eliminate apparent immediate hazards to the participants. 
For minor changes to a previously approved protocol during the period covered by the original 
approval, it may be possible for the investigator to obtain an expedited review by the IRB/IEC as 
allowed.
As part of the IRB/IEC requirements for continuing review of approved studies, the investigator 
will be responsible for submitting periodic progress reports to the IRB/IEC (based on IRB/IEC 
requirements), at intervals appropriate to the degree of participant risk involved, but no less than 
once per year. The investigator should provide a final report to the IRB/IEC following study 
completion.
UCB (or its representative) will communicate safety information to the appropriate regulatory 
authorities and all active investigators in accordance with applicable regulatory requirements. 
The appropriate IRB/IEC will also be informed by the investigator or the sponsor, as specified by 
the applicable regulatory requirements in each concerned country. Where applicable, 
investigators are to provide the sponsor (or its representative) with evidence of such IRB/IEC 
notification.
10.1.2
Financial disclosure
Insurance coverage will be handled according to local requirements.
Finance and insurance are addressed in the investigator and/or CRO agreements, as applicable.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 115 of 220
10.1.3
Informed consent process
Participant’s informed consent must be obtained and documented in accordance with local 
regulations, ICH-GCP requirements, and the ethical principles that have their origin in the 
principles of the Declaration of Helsinki.
Prior to obtaining informed consent, information should be given in a language and at a level of 
complexity understandable to the participant in both oral and written form by the investigator (or 
designee). Each participant will have the opportunity to discuss the study and its alternatives 
with the investigator.
Prior to participation in the study, the ICF should be signed and personally dated by the study 
participant, and by the person who conducted the informed consent discussion (investigator or 
designee) at the site. For Japan-specific regulations, see Appendix 8, Section 10.8. The study 
participant must receive a copy of the signed and dated ICF. As part of the consent process, each 
participant must consent to direct access to his/her medical records for study-related monitoring, 
auditing, IRB/IEC review, and regulatory inspection.
If the ICF is amended during the study, the investigator (or UCB, if applicable) must follow all 
applicable regulatory requirements pertaining to the approval of the amended ICF by the 
IRB/IEC and use of the amended form.
All studies conducted at centers in the United States must include the use of a Health Insurance 
Portability and Accountability Act Authorization form.
The participant may withdraw his/her consent to participate in the study at any time. A 
participant is considered as enrolled in the study when he/she has signed the ICF. An eCRF must 
not be started, nor may any study specific procedure be performed for a given participant, 
without having obtained his/her written consent to participate in the study.
10.1.4
Data protection
UCB staff (or designee) will affirm and uphold the participant’s confidentiality. Throughout this 
study, all data forwarded to UCB (or designee) will be identified only by the participant number 
assigned at Screening.
The investigator agrees that representatives of UCB, its designee, representatives of the relevant 
IRB/IEC, or representatives of regulatory authorities will be allowed to review that portion of the 
participant’s primary medical records that directly concerns this study (including, but not limited 
to, laboratory test result reports, ECG reports, admission/discharge summaries for hospital 
admissions occurring during a participant’s study participation, and autopsy reports for deaths 
occurring during the study).
The participant must be informed that his/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.
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 116 of 220
10.1.5
Committees structure
An external IDMC will be established to mainly review the safety data at predefined intervals 
and ad hoc as needed, should emerging safety concerns arise during the study. The IDMC will 
have the possibility to unblind the data. Details of the IDMC composition, processes, and 
responsibilities will be documented in the IDMC charter.
10.1.6
Data quality assurance
All participant data relating to the study will be recorded in the eCRF. The investigator is 
responsible for verifying that data entries are accurate and correct by electronically signing the 
eCRF.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF.
The investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents.
The sponsor or designee is responsible for the data management of this study including quality 
checking of the data.
Study monitors will perform ongoing source data verification to confirm that data entered into 
the eCRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.
All essential documents are to be retained by the investigator until at least 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the IMP. These documents should be retained 
for a longer period, however, if required by the applicable regulatory requirement(s) or by an 
agreement with UCB (CPMP/ICH/135/95, 2002 [Section 4.9.5]). The investigator will contact 
UCB for authorization prior to the destruction of any study records or in the event of accidental 
loss or destruction of any study records. The investigator will also notify UCB should he/she 
relocate or move the study-related files to a location other than that specified in the sponsor’s 
trial master file.
Quality tolerance limits will be established for the study using parameters related to patient 
safety reporting and reliability of study results. The parameters will be monitored throughout the 
study to identify systematic issues. Parameters used, parameter values, important deviations from 
the quality tolerance limits, and actions taken will be summarized in the clinical study report.
10.1.6.1
Electronic Case Report Form completion
The investigator is responsible for prompt reporting of accurate, complete, and legible data in the 
eCRFs and in all required reports.
Any change or correction to the eCRF after saving must be accompanied by a reason for the 
change.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 117 of 220
Corrections made after the investigator’s review and approval (by means of a 
password/electronic signature) will be reapproved by the investigator.
The investigator should maintain a list of personnel authorized to enter data into the eCRF.
Detailed instructions will be provided in the eCRF Completion Guidelines.
10.1.6.2
Apps
Not applicable.
10.1.7
Source documents
All source documents must be accurate, clear, unambiguous, permanent, and capable of being 
audited. They should be made using some permanent form of recording (ink, typing, printing, 
optical disc). They should not be obscured by correction fluid or have temporary attachments 
(such as removable self-stick notes). Photocopies and/or printouts of eCRFs are not considered 
acceptable source documents.
Source documents are original records in which raw data are first recorded. These may include 
hospital/clinic/general practitioner records, charts, diaries, x-rays, laboratory results, printouts, 
pharmacy records, care records, ECG or other printouts, completed scales, quality of life 
questionnaires, or video, for example. Source documents should be kept in a secure, limited 
access area.
The following data will be recorded directly in the eCRF and will not appear in a separate source 
document as defined above.
Source documents that are computer generated and stored electronically must be printed for 
review by the monitor (eg, ECG reports). Once printed, these copies should be signed and dated 
by the investigator and become a permanent part of the participant’s source documents. The 
investigator will facilitate the process for enabling the monitor to compare the content of the 
printout and the data stored in the computer to ensure all data are consistent.
Electronic data records, such as Holter monitor records or electroencephalogram records, must 
be saved and stored as instructed by UCB (or designee).
10.1.8
Study and site closure
The UCB designee reserves the right to close the study site or terminate the study at any time for 
any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to:
•
Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC or 
local health authorities, the sponsor's procedures, or GCP guidelines.
•
Inadequate recruitment of participants by the investigator.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 118 of 220
•
Discontinuation of further IMP development.
10.1.9
Publication policy
The results of this study may be published or presented at scientific meetings. If this is foreseen, 
the investigator agrees to submit all manuscripts or abstracts to the sponsor before submission. 
This allows UCB to protect proprietary information and to provide comments.
UCB will comply with the requirements for publication of study results. In accordance with 
standard editorial and ethical practice, UCB will generally support publication of multicenter 
studies only in their entirety and not as individual site data. In this case, a coordinating 
investigator will be designated by mutual agreement.
Authorship will be determined by mutual agreement and in line with International Committee of 
Medical Journal Editors authorship requirements.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 119 of 220
10.2
Appendix 2: Clinical laboratory tests
The tests detailed in Table 10-1 will be performed by the central laboratory, with the exception 
of platelet count assessments.
•
With the exception of platelet counts, local laboratory results are only required in the event 
that the central laboratory results are not available in time for either IMP administration 
and/or response evaluation. If a local sample is required, it is important that the sample for 
central analysis is obtained at the same time. Additionally, if the local laboratory results are 
used to make either a study treatment decision or response evaluation, the results must be 
entered into the eCRF.
•
Protocol-specific requirements for inclusion or exclusion of participants are detailed in 
Section 5.1 and Section 5.2 of the protocol, respectively.
•
Additional tests may be performed at any time during the study as determined necessary by 
the investigator or required by local regulations.
Table 10-1: Protocol-required safety laboratory assessments
Laboratory 
Assessments
Parameters
Hematology
Platelet Count (local 
laboratory) a
Red blood cell (RBC) Indices:
Mean corpuscular volume (MCV)
Mean corpuscular hemoglobin (MCH)
White blood cell 
(WBC) Count 
with Differential:
Neutrophils
Lymphocytes
Monocytes
Eosinophils
Basophils
RBC Count
Hemoglobin
Hematocrit
Coagulation
International 
Normalized Ratio 
(INR) d
Activated partial thromboplastin time 
(aPTT) e
Fibrinogen e
Clinical 
Chemistry f
Blood Urea 
Nitrogen (BUN)
Potassium
Aspartate 
Aminotransferase 
(AST)/Serum 
Glutamic-Oxaloacetic 
Transaminase (SGOT)
Total and direct 
bilirubin
Creatinine
Sodium
Alanine 
Aminotransferase 
(ALT)/Serum 
Glutamic-Pyruvic 
Transaminase (SGPT)
Total Protein
Glucose (fasting 
state preferred)
Calcium
Alkaline phosphatase
C-reactive protein 
(CRP)
Immunoglobulins g
Albumin
Low-density lipoprotein 
(LDL)
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 120 of 220
Laboratory 
Assessments
Parameters
High-density lipoprotein 
(HDL)
Total cholesterol
Triglycerides
Routine 
Urinalysis
•
Specific gravity
•
pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte 
esterase by dipstick
•
Microscopic examination (if blood or protein is abnormal)
Other 
Screening 
Tests
•
Follicle-stimulating hormone and estradiol (as needed in women of 
non-childbearing potential only)
•
Serum or urine human chorionic gonadotropin (hCG) pregnancy test (as needed 
for women of childbearing potential) h
•
Serology (human immunodeficiency [HIV] antibody, hepatitis B surface antigen 
[HBsAg], and hepatitis C virus antibody)
•
All study-required laboratory assessments will be performed by a central 
laboratory except the platelet count which is done by local laboratory.
•
The results of each test must be entered into the electronic Case Report Form 
(eCRF).
a Platelet count testing will be performed by a local laboratory. Results will be unblinded to the investigator, site, 
and study participant (see Section 6.2.1.1).
b International Normalized Ratio (INR) to be done only at Screening (Visit 1) and for PDILI.
c Activated partial thromboplastin time (aPTT) and Fibrinogen will be done at all visits which require safety 
laboratory assessments.
d Details of liver chemistry stopping criteria and required actions and follow-up assessments after liver stopping 
or monitoring event are given in Section 7.1.1 and Appendix 6, Section 10.6. All events of ALT 3x upper limit 
of normal (ULN) and bilirubin 2xULN (>35% direct bilirubin) or ALT 3xULN and international normalized 
ratio (INR) >1.5, if INR measured, may indicate severe liver injury (possible Hy’s Law) and must be reported 
as a serious adverse event (SAE) (excluding studies of hepatic impairment or cirrhosis).
e Includes total IgG, IgG subclasses, IgA, IgM, and IgE. Results of the IgG testing including the vaccination 
specific titers will be blinded to the investigator, site, and sponsor for post baseline results.
f Local urine testing will be standard for the protocol unless serum testing is required by local regulation or 
Independent Review Board/Independent Ethics Committee.
Investigators must document their review of each laboratory safety report.
Laboratory/analyte results that could unblind the study will not be reported to study sites or other 
blinded personnel until the study has been unblinded.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 121 of 220
10.3
Appendix 3: Adverse events – definitions and procedures for 
recording, evaluating, follow up, and reporting
10.3.1
Definition of AE
Adverse event (AE) Definition
•
An AE is any untoward medical occurrence in a patient or clinical study participant, 
temporally associated with the use of IMP, whether or not considered related to the IMP.
•
NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of IMP.
Events Meeting the AE Definition
•
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (eg, ECG, radiological scans, vital signs measurements), 
including those that worsen from Baseline, considered clinically significant in the medical 
and scientific judgment of the investigator (ie, not related to progression of underlying 
disease).
•
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition.
•
New conditions detected or diagnosed after IMP administration even though it may have 
been present before the start of the study.
•
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.
•
Signs, symptoms, or the clinical sequelae of a suspected overdose of either IMP or a 
concomitant medication. Overdose per se will not be reported as an AE/serious AE (SAE) 
unless it is an intentional overdose taken with possible suicidal/self-harming intent. Such 
overdoses should be reported regardless of sequelae.
•
"Lack of efficacy" or "failure of expected pharmacological action" per se will not be 
reported as an AE or SAE. Such instances will be captured in the efficacy assessments. 
However, the signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will 
be reported as AE or SAE if they fulfil the definition of an AE or SAE.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 122 of 220
Events NOT Meeting the AE Definition
•
Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition.
•
The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the study participant’s 
condition.
•
Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to 
the procedure is the AE.
•
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).
•
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen.
10.3.2
Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (eg, hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease).
A SAE is defined as any untoward medical occurrence that, at any dose:
a.
Results in death
b.
Is life-threatening
The term “life-threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, which 
hypothetically might have caused death, if it were more severe.
c.
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the participant has been detained (usually involving at 
least an overnight stay) at the hospital or emergency ward for observation and/or treatment that 
would not have been appropriate in the physician’s office or outpatient setting. Complications 
that occur during hospitalization are AEs. If a complication prolongs hospitalization or fulfills 
any other serious criteria, the event is serious. When in doubt as to whether “hospitalization” 
occurred or was necessary, the AE should be considered serious.
Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
Baseline is not considered an AE.
d.
Results in persistent disability/incapacity
•
The term disability means a substantial disruption of a person’s ability to conduct normal 
life functions.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 123 of 220
•
This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenzae, and 
accidental trauma (eg, sprained ankle) which may interfere with or prevent everyday life 
functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Important medical events:
•
Medical or scientific judgment should be exercised in deciding whether SAE reporting is 
appropriate in other situations such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize the 
participant or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition. These events should usually be considered serious.
Examples of such events include, but are not limited to potential Hy’s law, invasive or 
malignant cancers, 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.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 124 of 220
10.3.3
Recording and Follow up of AE and/or SAE
AE and SAE Recording
•
When an AE/SAE occurs, it is the responsibility of the investigator to review all
documentation (eg, hospital progress notes, laboratory reports, and diagnostics reports) 
related to the event.
•
The investigator will then record all relevant AE/SAE information in the eCRF.
•
It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to UCB in lieu of completion of the UCB AE/SAE eCRF page.
•
There may be instances when copies of medical records for certain cases are requested by 
UCB. In this case, all participant identifiers, with the exception of the participant number, 
will be redacted on the copies of the medical records before submission to UCB.
•
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not the 
individual signs/symptoms) will be documented as the AE/SAE.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported during 
the study and assign it to 1 of the following categories:
•
Mild: An event that is easily tolerated by the participant, causing minimal discomfort and 
not interfering with everyday activities.
•
Moderate: An event that causes sufficient discomfort and interferes with normal everyday 
activities.
•
Severe: An event that prevents normal everyday activities. An AE that is assessed as 
severe should not be confused with a SAE. Severe is a category utilized for rating the 
intensity of an event; and both AEs and SAEs can be assessed as severe.
•
An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe (eg, a severe AE may 
be either serious or not serious, depending on whether these criteria are also met).
The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-
CTCAE) should be used as a supportive standardization instrument to evaluate AEs and SAEs 
but the final intensity grading by the investigator must be mild, moderate, or severe.
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03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 125 of 220
Assessment of Causality
•
The investigator is obligated to assess the relationship between IMP and each occurrence 
of each AE/SAE.
•
A "reasonable possibility" of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out.
•
The investigator will use clinical judgment to determine the relationship.
•
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to IMP administration will be 
considered and investigated.
•
The investigator will also consult the Investigator’s Brochure (IB) and/or Product 
Information, for marketed products, in his/her assessment.
•
For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality.
•
There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to UCB. However, it is very important that the 
investigator always makes an assessment of causality for every event before the initial 
transmission of the SAE data to UCB.
•
The investigator may change his/her opinion of causality in light of follow-up information 
and send a SAE follow-up report with the updated causality assessment.
•
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements.
Follow-up of AEs and SAEs
•
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by UCB to 
elucidate the nature and/or causality of the AE or SAE as fully as possible. This may 
include additional laboratory tests or investigations, histopathological examinations, or 
consultation with other health care professionals.
•
An AE should be followed until it has resolved, has a stable sequelae, the investigator 
determines that it is no longer clinically significant, the event is otherwise explained, or the 
participant is lost to follow up. This follow-up requirement applies to AEs, SAEs, and AEs 
of special interest.
•
If a participant dies during participation in the study or during a recognized Follow-up 
Period, the investigator will provide UCB with a copy of any post-mortem findings 
including histopathology.
•
New or updated information will be recorded in the originally completed eCRF.
•
The investigator will submit any updated SAE data to UCB within 24 hours of receipt of 
the information.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 126 of 220
10.3.4
Reporting of SAEs
SAE Reporting to UCB via an Electronic Data Collection Tool
•
The primary mechanism for reporting an SAE to UCB will be the electronic data collection 
tool.
•
If the electronic system is unavailable for more than 24 hours, then the site will use the 
paper SAE data collection tool (see “SAE Reporting to UCB via Paper Case Report Form 
[CRF]” below).
•
The site will enter the SAE data into the electronic system as soon as it becomes available.
•
After the study is completed at a given site, the electronic data collection tool will be taken 
off-line to prevent the entry of new data or changes to existing data.
•
If a site receives a report of a new SAE from a study participant or receives updated data 
on a previously reported SAE after the electronic data collection tool has been taken off-
line, then the site can report this information on a paper SAE form (see “SAE Reporting to 
UCB via Paper CRF” below).
•
Contacts for SAE reporting can be found in SERIOUS ADVERSE EVENT REPORTING.
SAE Reporting to UCB via Paper CRF
•
Facsimile transmission of the SAE paper CRF is the preferred method to transmit this 
information to UCB; see SERIOUS ADVERSE EVENT REPORTING.
•
In rare circumstances and in the absence of facsimile equipment, notification by telephone 
is acceptable with a copy of the SAE data collection tool sent by overnight mail or courier 
service.
•
Initial notification via telephone does not replace the need for the investigator to complete 
and sign the SAE CRF pages within the designated reporting time frames.
•
Contacts for SAE reporting can be found in SERIOUS ADVERSE EVENT REPORTING.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 127 of 220
10.4
Appendix 4: Contraceptive guidance and collection of 
pregnancy information
Definitions
Woman of childbearing potential (WOCBP)
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile (see below).
Women in the following categories are not considered WOCBP:
1. Premenarchal
2. Premenopausal female with 1 of the following:
−
Documented hysterectomy
−
Documented bilateral salpingectomy
−
Documented bilateral oophorectomy
Note: Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview.
3. Postmenopausal female 
−
A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. A high follicle stimulating hormone (FSH) level (>40mIU/mL) in the 
postmenopausal range may be used to confirm a postmenopausal state in women not 
using hormonal contraception or hormonal replacement therapy (HRT). However, in the 
absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
−
Females on HRT and whose menopausal status is in doubt will be required to use one of 
the non-estrogen hormonal highly effective contraception methods if they wish to 
continue their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before study enrollment.
Contraception guidance
Male participants
Male participants with female partners of childbearing potential are eligible to participate if they 
agree to ONE of the following during the Treatment Period and for at least 3 months after the 
final dose of study treatment:
•
Are abstinent from penile-vaginal intercourse as their usual and preferred lifestyle (abstinent 
on a long term and persistent basis) and agree to remain abstinent.
•
Agree to use a male condom when having penile-vaginal intercourse with a woman of 
childbearing potential who is not currently pregnant.
In addition, male participants must refrain from donating sperm for the duration of the study and 
for 3 months after the final dose of study medication.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 128 of 220
Male participants with a pregnant or breastfeeding partner must agree to remain abstinent from 
penile-vaginal intercourse or use a male condom during each episode of penile penetration 
during the Treatment Period and for at least 3 months after the final dose of study treatment.
Female participants
Female participants of childbearing potential are eligible to participate if they agree to use a 
highly effective method of contraception consistently and correctly as described in Table 10-2.
Table 10-2: Highly effective contraceptive methodsa
Highly Effective Contraceptive Methods That Are User Dependentb
Failure rate of <1% per year when used consistently and correctly.
Combined (estrogen- and progesterone-containing) hormonal contraception associated with 
inhibition of ovulation
• Oral
• Intravaginal
• Transdermal
Progesterone only hormonal contraception associated with inhibition of ovulation
• Oral
• Injectable
Highly Effective Methods That Are User Independent
Implantable progesterone only hormonal contraception associated with inhibition of ovulation
• Intrauterine device (IUD)
• Intrauterine hormone-releasing system (IUS)
• Bilateral tubal occlusion
Vasectomized partner
Vasectomy is a highly effective contraception method provided that the vasectomized partner is 
the sole male 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. For Japan-specific 
regulations, see Appendix 8, Section 10.8
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 medication. 
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.
a In case of newly started contraception pills/IUDs, the primary investigator should consider the correct timing of 
starting/applying such methods in relation to the menstrual cycle and the manufacturing instruction as when these 
newly started methods would become effective.
b Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent 
with local regulations regarding the use of contraceptive methods for participants in clinical studies.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 129 of 220
Pregnancy testing
•
WOCBP should only be included after a confirmed menstrual period and a negative highly 
sensitive urine pregnancy test.
•
Additional urine pregnancy testing should be performed at time points specified in the 
Schedule of Activities (Section 1.3) and as required locally.
•
Pregnancy testing will be performed whenever a menstrual cycle is missed or when 
pregnancy is otherwise suspected.
•
Pregnancy testing with a sensitivity of 25mIU/mL will be performed. A serum pregnancy test 
will be performed to confirm a positive urine pregnancy test.
Male participants with partners who become pregnant
•
The investigator will attempt to collect pregnancy information on any male participant’s 
female partner who becomes pregnant while the male participant is in this study. This applies 
only to male participants who receive IMP.
•
After obtaining the necessary signed informed consent from the pregnant female partner 
directly, the investigator will record pregnancy information on the appropriate form and 
submit it to the sponsor within one working day of learning of the partner’s pregnancy. The 
female partner will also be followed to determine the outcome of the pregnancy. Information 
on the status of the mother and child will be forwarded to the sponsor. Generally, the follow-
up will be at least 12 months after the delivery date. Any termination of the pregnancy will 
be reported regardless of fetal status (presence or absence of anomalies) or indication for the 
procedure.
Female participants who become pregnant
•
Any female participant who becomes pregnant while participating in the study will be 
withdrawn from the study
•
The investigator will collect pregnancy information on any female participant who becomes 
pregnant while participating in this study. Information will be recorded on the appropriate 
form and submitted to the sponsor within one working day of learning of a participant's 
pregnancy. The participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow-up information on the participant and the neonate and the 
information will be forwarded to the sponsor. Generally, the follow-up will be at least 
12 months after the delivery date. Any termination of pregnancy will be reported, regardless 
of fetal status (presence or absence of anomalies) or indication for the procedure.
•
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy will be reported as an AE or SAE. A spontaneous 
abortion is always considered to be an SAE and will be reported as such. Any post-study 
pregnancy-related SAE considered reasonably related to the IMP by the investigator will be 
reported to the sponsor as described in Section 8.3.5. While the investigator is not obligated 
to actively seek this information in former study participants, he or she may learn of an SAE 
through spontaneous reporting.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 130 of 220
10.5
Appendix 5: Genetics
Use and Analysis of DNA
•
Genetic variation may impact a participant’s response to IMP, susceptibility to, and severity 
and progression of disease. Variable response to IMP may be due to genetic determinants 
that impact drug absorption, distribution, metabolism, and excretion; mechanism of action of 
the drug; disease etiology; and/or molecular subtype of the disease being treated. Therefore, 
where local regulations and IRB/IEC allow, a blood sample will be collected for 
deoxyribonucleic acid (DNA) analysis from consenting participants.
•
DNA samples will be used for research related to cause, progression, and appropriate 
treatment of ITP. They may also be used to develop tests/assays including diagnostic tests 
related to rozanolixizumab and ITP. Genetic research may consist of the analysis of 1 or 
more candidate genes or the analysis of genetic markers throughout the genome.
•
The samples may be analyzed as part of a multi-study assessment of genetic factors involved 
in the response to rozanolixizumab or IMPs of this class to understand ITP or related 
conditions.
•
The results of genetic analyses may be reported in the clinical study report or in a separate 
study summary.
•
The sponsor will store the DNA samples in a secure storage space with adequate measures to 
protect confidentiality.
•
The samples will be retained while research on rozanolixizumab continues, but no longer 
than 20 years or other period as per local requirements.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 131 of 220
10.6
Appendix 6: Liver safety – suggested actions and follow-up 
assessments
Study treatment, including all concomitant medications and herbal supplements that are not 
medically necessary, should be discontinued immediately in study participants with suspected 
PDILI. These study participants must be assessed thoroughly and followed up closely during the 
Treatment Period for confirmation of PDILI. Because study participants in TP0003 will be 
provided the chance to enroll in the OLE study TP0004 upon completion of TP0003, if PDILI is 
confirmed, these study participants must not be enrolled in the OLE study TP0004.
Investigators should attempt to obtain information on study participants to complete the final 
evaluation.
Study participants with PDILI should not be withdrawn from the study until investigation and 
monitoring are complete. All results of these evaluations and observations, as well as the 
reason(s) for study participant withdrawal (if applicable, eg, withdrawal of consent), must be 
recorded in the source documents. The eCRF must document the primary reason for study 
withdrawal in such a case.
A specific monitoring plan must be agreed between the UCB study physician and the 
investigator for study participants who have ALT >5 ULN. The monitoring plan should include 
any necessary follow-up assessments (until resolution of the abnormal lab values).
Phase 3-4 liver chemistry stopping criteria are designed to assure participant safety and to 
evaluate liver event etiology (Table 10-3).
Phase 3-4 liver chemistry increased monitoring criteria with continued IMP are designed to 
assure participant safety and to evaluate liver event etiology (Table 10-4). 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 132 of 220
Table 10-3: Phase 3-4 liver chemistry stopping criteria and follow-up 
assessments
Liver Chemistry Stopping Criteria
ALT-absolute
ALT 8xULN
ALT Increase
ALT 5xULN but <8xULN persists for 2 weeks
ALT 3xULN but <5xULN persists for 4 weeks
Bilirubin a b
ALT 3xULN and bilirubin 2xULN (>35% direct bilirubin) 
INR b
ALT 3xULN and international normalized ratio (INR) >1.5, if INR measured
Cannot 
Monitor
ALT 5xULN but <8xULN and cannot be monitored weekly for 2 weeks
ALT 3xULN but <5xULN and cannot be monitored weekly for 4 weeks
Symptomatic c
ALT 3xULN associated with symptoms (new or worsening) believed to be related 
to liver injury or hypersensitivity
Suggested Actions and Follow-Up Assessments
Actions
Follow-Up Assessments
•
Immediately discontinue IMP.
•
Report the event to UCB within
24 hours.
•
Complete the liver event electronic Case 
Report Form (eCRF), and complete a 
serious adverse event (SAE) data 
collection tool if the event also met the 
criteria for an SAE. b
•
Perform liver chemistry follow-up 
assessments. 
•
Monitor the participant until liver 
chemistry test abnormalities resolve, 
stabilize, or return to Baseline (see 
MONITORING).
•
Do not restart/rechallenge participant 
with IMP unless allowed per protocol 
and UCB approval is granted.
If restart/rechallenge not allowed per protocol 
or not granted, permanently discontinue IMP 
and continue participant in the study for any 
protocol specified follow up assessments. 
Consider the need for a toxicology screening.
MONITORING:
For bilirubin or INR criteria:
•
Viral hepatitis serology d
•
Obtain INR and recheck with each liver 
chemistry assessment until the 
transaminases values show downward 
trend
•
Only in those with underlying chronic 
hepatitis B at study entry (identified by 
positive hepatitis B surface antigen), 
quantitative hepatitis B deoxyribonucleic 
acid (DNA) and hepatitis delta antibody e
•
Obtain blood sample for pharmacokinetic 
(PK) analysis as soon as feasible after the 
most recent dose f
•
Serum creatine phosphokinase (CPK) and 
lactate dehydrogenase (LDH)
•
Fractionate bilirubin, if total bilirubin 
2xULN
•
Obtain complete blood count with 
differential to assess eosinophilia
•
Record the appearance or worsening of 
clinical symptoms of liver injury, or 
hypersensitivity, on the adverse event (AE) 
report form
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 133 of 220
•
Repeat liver chemistry tests (include 
ALT, aspartate transaminase [AST], 
alkaline phosphatase, bilirubin) and 
perform liver event follow-up 
assessments within 24 hours.
•
Monitor participant twice weekly until 
liver chemistry test abnormalities 
resolve, stabilize, or return to Baseline.
•
A specialist or hepatology consultation is 
recommended.
For all other criteria
•
Repeat liver chemistry tests (include 
ALT, AST, alkaline phosphatase, 
bilirubin) and perform liver chemistry 
follow-up assessments within 24 to 72 
hours.
•
Monitor participants weekly until liver 
chemistry abnormalities resolve, 
stabilize, or return to Baseline.
•
Record use of concomitant medications 
(including acetaminophen, herbal 
remedies, and other over-the-counter 
medications) on the concomitant 
medications eCRF.
•
Record alcohol use on the liver event 
alcohol intake eCRF
•
Exclude pregnancy
For bilirubin or INR criteria:
•
Anti-nuclear antibody, anti-smooth muscle 
antibody, Type 1 anti-liver kidney 
microsomal antibodies, and quantitative 
total immunoglobulin G (IgG) or gamma 
globulins g
•
Serum acetaminophen concentration and 
serum acetaminophen adduct assay (where 
available) for assessing the potential 
acetaminophen contribution to liver injury. 
•
Liver imaging (ultrasound, magnetic 
resonance, or computerized tomography) 
and/or liver biopsy to evaluate liver 
disease; complete Liver Imaging and/or 
Liver Biopsy eCRFs
a Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue IMP if ALT ≥3xULN and bilirubin ≥2xULN. Additionally, if serum 
bilirubin fractionation testing is unavailable, record the absence/presence of detectable urinary bilirubin on 
dipstick, which is indicative of direct bilirubin elevations suggesting liver injury.
b All events of ALT ≥3xULN and bilirubin ≥2xULN (>35% direct bilirubin) or ALT ≥3xULN and INR >1.5 
may indicate severe liver injury (possible ‘Hy’s Law’) and must be reported as an SAE (excluding studies 
of hepatic impairment or cirrhosis). The INR measurement is not required, and the stated threshold value will 
not apply to participants receiving anticoagulants.
c New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right 
upper quadrant pain or tenderness, or jaundice) or hypersensitivity (such as fever, rash or eosinophilia).
d Includes: Hepatitis A immunoglobulin M (IgM) antibody; HBsAg and HBcAb; hepatitis C RNA; 
cytomegalovirus IgM antibody; Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, heterophile 
antibody or monospot testing); and hepatitis E IgM antibody.
e If hepatitis delta antibody assay cannot be performed, it can be replaced with a polymerase chain reaction (PCR) 
of hepatitis D RNA virus (where needed) [Le Gal, 2005].
f Pharmacokinetic sample may not be required for participants known to be receiving placebo or non-comparator 
interventions. Record the date/time of the PK blood sample draw and the date/time of the final dose of IMP 
prior to the PK blood sample draw on the eCRF. If the date or time of the final dose is unclear, provide the 
participant’s best approximation. If the date/time of the final dose cannot be approximated OR a PK sample 
cannot be collected in the time period indicated above, do not obtain a PK sample. Instructions for sample 
handling and shipping are in the Pharmacy Manual.
g These tests should be obtained when IgG levels are approaching normal levels because IMP may interfere with 
IgG levels and interpretation.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 134 of 220
Table 10-4: Phase 3-4 liver chemistry increased monitoring criteria with 
continued IMP
Liver Chemistry Increased Monitoring Criteria
Criteria
Actions
ALT 5xULN and <8xULN and
bilirubin <2xULN without symptoms 
believed to be related to liver injury or 
hypersensitivity, and who can be 
monitored weekly for 2 weeks.
OR
ALT 3xULN and <5xULN and
bilirubin <2xULN without symptoms 
believed to be related to liver injury or 
hypersensitivity, and who can be 
monitored weekly for 4 weeks.
•
Notify the UCB Medical Monitor within 
24 hours of learning of the abnormality to discuss 
participant safety.
•
Participant can continue IMP
•
Participant must return weekly for repeat liver 
chemistry tests (ALT, AST, alkaline phosphatase, 
bilirubin) until the abnormalities resolve, 
stabilize, or return to Baseline.
•
If at any time, the participant meets liver 
chemistry stopping criteria, proceed as described 
in Section 7.1.1.
•
If ALT decreases from ALT 5xULN and
<8xULN to ≥3xULN but <5xULN, continue to 
monitor liver chemistries weekly.
•
If, after 4 weeks of monitoring, ALT <3xULN 
and bilirubin <2xULN, monitor participants twice 
monthly until liver chemistry tests resolve, 
stabilize, or return to Baseline.
REFERENCES
Le Gal F, Gordien E, Affolabi D, Hanslik T, Alloui C, Dény P, Gault E. Quantification of 
Hepatitis Delta Virus RNA in Serum by Consensus Real-Time PCR Indicates Different Patterns 
of Virological Response to Interferon Therapy in Chronically Infected Patients. J Clin Microbiol. 
2005;43(5):2363–2369.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 135 of 220
10.7
Appendix 7: Medical device incidents – definition and 
procedures for recording, evaluating, follow up, and reporting
Not applicable.
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof. 


UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 136 of 220
10.8
Appendix 8: Country-specific requirements
Moldova
Specific requirements for study participants in Moldova include a description of vaccination for 
splenectomized study participants who have not received vaccinations according to current 
medical practice and are being considered for the study. Vaccinations in splenectomized patients 
are not routinely performed in Moldova, and the patients likely carry an undeterminable 
increased risk for infections. Hence, study participants who are being considered for the study 
will be administered vaccines accordingly to the schedule as per Table 1-3.
Poland
The Polish Health Authority’s and Clinical Trial Facilitation Group have made recommendations 
related to contraception and pregnancy testing in a clinical study with IMP where the human data 
for exposure at pregnancy and nonclinical reproductive toxicology data are not available. As a 
mitigation measure, pregnancy testing is to be implemented monthly up to 2 months after the 
final dose of IMP. A urine pregnancy test is added at 4 weeks after final IMP administration, at 
Week 27 (Visit 28) for sites located in Poland, thus it meets the above requirement. Based on the 
short half-life of IMP and because genotoxicity is not a class effect of the monoclonal antibodies, 
it is considered safe to reduce the duration of post-IMP administration requirement on 
contraception for female study participants of childbearing potential from 3 months to 2 months, 
with implementation of monthly pregnancy testing during this period.
Romania
Previously, in TP0001, the Romanian authorities introduced the following specific requirement 
for Romania: change in duration for the use of permitted oral corticosteroids (prednisolone) from 
a stable dose of 
 prior to the Baseline Visit (Visit 2). It is recommended for 
sites located in Romania, that oral corticosteroids (prednisone) need to be stable for 
 as mentioned in Table 6-2 of this protocol.
Japan
Specific requirements for study participants in Japan include:
•
In reference to Section 5.1, inclusion criteria 1 has been modified as shown below:
1a. Study participant must be ≥18 years of age at the time of the Screening Visit. If a 
participant is <20 years of age, written informed consent will be obtained from both the 
participant and the legal representative.
•
In reference to Section 5.2, exclusion criteria 7 has been modified as shown below:
7a. Study participant has evidence of a secondary cause of immune thrombocytopenia (eg, past 
medical history of untreated H. pylori infection, leukemia, lymphoma, common variable 
immunodeficiency, systemic lupus erythematosus, autoimmune thyroid disease) or 
participant has a multiple immune cytopenia, eg, Evan’s syndrome.
•
In reference to Section 5.2, exclusion criteria 20a has been modified as shown below:
20b.Splenectomized participant without adequate vaccination against S. pneumoniae, 
N. meningitidis and H. influenzae, if applicable per local guidance, and as evidenced by: 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 137 of 220
-
a lack of documented vaccination records per local guidance, OR
have not completed required vaccinations (S. pneumoniae, H. influenzae, and N. 
meningitidis) per Section 8.2.6 during the Prolonged Screening Period
Note: For splenectomized participants without any prior vaccination against one or all of the 
above-mentioned bacteria please refer to Section 8.2.6 of the protocol.
•
In reference to Section 5.2, exclusion criteria 44 has been added:
44. Study participant has undergone a partial splenic artery embolization in the 6 months prior to 
Baseline Visit. Any study participant with evidence of functional asplenia should be 
managed clinically as a splenectomized participant (eg, vaccination, antibiotics prophylaxis) 
as per local guidance.
•
A new section (Section 6.1 Medical Devices) was added in Protocol Amendment 1.2 and has 
now been updated to the following:
Applicable to Japan only
UCB will supply the study-sites with the Crono S-PID pump (manufactured by Cané S.r.L, 
Torino, Italy) and the Cleo 90 infusion set (manufactured by Smith’s Medical ASD Inc, St Paul, 
MN, USA) for the subcutaneous infusion.
Both the Crono syringe driver and the Cleo 90 infusion set used for the purpose of sc infusions 
are regarded in Japan as investigational devices, that require adherence to specific reporting 
obligations (Appendix 8, Section 10.8). This reporting requirement is not applicable for 
approved devices for the purpose of sc infusions or other purposes in the course of this study, 
regardless if provided by the sponsor or not.
All adverse device effects (ADEs), serious adverse device effects (SADEs), and medical device 
deficiency (including malfunction use error, and inadequate labeling) of these investigational 
devices shall be documented and reported by the Investigator throughout the study (Appendix 8, 
Section 10.8) and appropriately managed by the Sponsor.
•
In reference to Section 6.4.1, the use of medicinal cannabidiols and medicinal marijuana are 
prohibited by law.
•
In reference to Section 8.2.6, additional wording has been included: “if applicable” and “as 
per local requirements”.
Vaccination for splenectomized participant will be carried out in accordance with local guidance 
(Kashiwagi, 2019).
•
In reference to Section 10.1.3 the following has been added:
In Japan, for all study participants <20 years of age, written informed consent will be obtained 
from both the participant and the legal representative.
•
In reference to Section 10.4, Table 10-2 the following method has been added: 
“(eg, proper use of condom in combination with spermicide)”
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 138 of 220
Furthermore, specific rules for repetition of an ADE and device deficiency should be followed 
by all study sites in Japan; this requirement is not applicable for locally approved devices, 
regardless if provided by the sponsor or not.
For ADEs and/or device deficiencies that are not related to the natural course of the disease 
under study, an increase in the intensity of the original ADE, and/or device deficiency should 
lead to the repetition of the original ADE and/or device deficiency with the following guidelines:
•
The outcome date of the original ADE and/or device deficiency must be the same as the start 
date of the repeated ADE and/or device deficiency.
•
The outcome of the original ADE and/or device deficiency must be recorded as “worsening.”
•
The verbatim term for the repeated ADE and/or device deficiency must be the same as the 
verbatim term for the original ADE and/or device deficiency so that the repeated ADE and/or 
device deficiency is obviously a worsening of the original.
As per local requirements in Japan, SAEs associated to an investigational device, and device 
deficiencies (eg, infusion pump product provided from sponsor) should be reported in 
accordance with the following. 
This requirement is not applicable for approved devices used in the course of the study, 
regardless if provided by the sponsor or not.
Medical Device – Adverse events (ADEs, SAEs, and SADEs) and device 
deficiencies
Medical devices are being provided for use in this study for subcutaneous infusions. In order to 
fulfill regulatory reporting obligations worldwide, the investigator is responsible for the detection 
and documentation of events meeting the definitions of incident or malfunction that occur during 
the study with such devices. 
Adverse events will be reported according to the ISO 14155:2011, while recognizing and 
following requirements including reporting timelines specified in other specific laws, 
regulations, directives, standards and/or guidelines as appropriate and as required by the 
countries in which the clinical investigation is conducted. 
NOTE: Events fulfilling the definition of an AE/SAE will also follow the processes outlined in 
Section 8.3.3 and Appendix 3 (Section 10.3) of the protocol.
Time period for detecting medical device deficiencies
Medical device deficiency or malfunction of the device that results in a reportable event will be 
detected, documented, and reported during all periods of the study in which the medical device is 
used. 
If the investigator learns of any deficiency at any time after a participant has been discharged 
from the study, and such event(s) is considered reasonably related to a medical device provided 
for the study, the investigator will promptly notify the sponsor.
Follow-up of medical device deficiencies
Follow-up applies to all study participants, including those who discontinue study medication 
and/or the study.
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03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 139 of 220
The investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the deficiency.
New or updated information will be recorded on the originally completed form with all changes 
signed and dated by the investigator.
Prompt reporting of medical device deficiencies to sponsor
Device deficiencies will be reported to the sponsor within 24 hours after the investigator 
determines that the event meets the protocol definition of a medical device deficiency.
The Adverse Event and Device Deficiency Report Form will be sent to the sponsor by email. If 
email is unavailable, then fax should be utilized.
The sponsor will be the contact for the receipt of device deficiency reports.
Regulatory reporting requirements for medical device deficiencies
The investigator will promptly report all device deficiencies occurring with any medical device 
provided for use in the study in order for the sponsor to fulfill the legal responsibility to notify 
appropriate regulatory authorities and other entities about certain safety information relating to 
medical devices being used in clinical studies.
The investigator, or responsible person according to local requirements (eg, the head of the 
medical institution) will comply with the applicable local regulatory requirements relating to the 
reporting of device deficiencies to the IRB/IEC.
Medical Device AEs (ADEs, UADEs, SAEs, SADEs, and USADEs) and device 
deficiencies: Definition and procedures for recording, evaluating, follow-up, and 
reporting
The definitions and procedures detailed in this appendix are in accordance with ISO 14155.
Both the investigator and the sponsor will comply with all local medical device reporting 
requirements.
The detection and documentation procedures described in this protocol apply to all sponsor 
medical devices provided for use in the study. 
Definition of AE and ADE
AE and ADE Definition 
•
An AE is any untoward medical occurrence, in a patient or clinical study participant, 
temporarily associated with the use of IMP, whether or not considered related to the IMP. 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the 
use of IMP.
•
An adverse device effect (ADE) is defined as an adverse event related to the use of an 
investigational medical device. This definition includes any adverse events resulting from 
insufficient or inadequate instructions for use, deployment, implantation, installation, or 
operation, or any malfunction of the investigational medical device as well as any event 
resulting from use error or from intentional misuse of the investigational medical device.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 140 of 220
Definition of SAE, and SADE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (eg, hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease).
An SAE is an AE that:
a.
Results in death 
b.
Is life-threatening
The term ‘life-threatening' in the definition of serious' refers to an event in which the participant 
was at risk of death at the time of the event. It does not refer to an event, which hypothetically 
might have caused death, if it were more severe.
c.
Requires inpatient or prolongation of existing hospitalization.
In general, hospitalization signifies that the participant has been detained (usually involving at least 
an overnight stay) at the hospital or emergency ward for observation and/or treatment that would 
not have been appropriate in the physician's office or outpatient setting. Complications that occur 
during hospitalization are AEs. If a complication prolongs hospitalization or fulfils any other 
serious criteria, the event is serious. When in doubt as to whether "hospitalization" occurred or was 
necessary, the AE should be considered serious.
Hospitalization for elective treatment of a pre-existing condition that did not worsen from Baseline 
is not considered an AE.
d.
Results in persistent disability/incapacity
The term disability means a substantial disruption of a person's ability to conduct normal life 
functions.
This definition is not intended to include experiences of relatively minor medical significance such 
as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma (eg, 
sprained ankle) which may interfere with or prevent everyday life functions but do not constitute a 
substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Important medical events
Medical or scientific judgment should be exercised in deciding whether SAE reporting is 
appropriate in other situations such as important medical events that may not be immediately life-
threatening or result in death or hospitalization but may jeopardize the participant or may require 
medical or surgical intervention to prevent one of the other outcomes listed in the above definition. 
These events should usually be considered serious.
Examples of such events include, but are not limited to, potential Hy’s law, invasive or malignant 
cancers, 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.
SADE definition
•
A SADE is defined as an adverse device effect that has resulted in any of the consequences 
characteristic of a serious adverse event.
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03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 141 of 220
Definition of Device Deficiency
Device Deficiency definition
•
A device deficiency is an inadequacy of an investigational medical device with respect to its 
identity, quality, durability, reliability, safety, or performance. Device deficiencies include 
malfunctions, use errors, and inadequate labeling.
Recording and Follow-Up of AE and/or SAE and Device Deficiencies
AE, SAE and Device Deficiency Recording
•
When an AE/SAE/device deficiency occurs, it is the responsibility of the investigator to review 
all documentation (eg, hospital progress notes, laboratory reports, and diagnostics reports) 
related to the event.
•
The investigator will then record all relevant AE/SAE/device deficiency information in the 
participant’s medical records, in accordance with the investigator’s normal clinical practice and 
on the appropriate form of the CRF.
•
It is not acceptable for the investigator to send photocopies of the participant’s medical records 
to UCB in lieu of completion of the AE/SAE/device deficiency CRF page.
•
There may be instances when copies of medical records for certain cases are requested by 
UCB. In this case, all participant identifiers, with the exception of the participant number, will 
be redacted on the copies of the medical records before submission to UCB.
•
The investigator will attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information. Whenever possible, the diagnosis (not the individual 
signs/symptoms) will be documented as the AE/SAE.
•
For device deficiencies, it is very important that the investigator describes any corrective or 
remedial actions taken to prevent recurrence of the deficiency
o
A remedial action is any action other than routine maintenance or servicing of a 
medical device where such action is necessary to prevent recurrence of a device 
deficiency. This includes any amendment to the device design to prevent recurrence. 
The investigator should inform the sponsor for all reported device deficiencies. 
Follow-up of AE/SAE/device deficiency
•
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by UCB to elucidate 
the nature and/or causality of the AE/SAE/device deficiency as fully as possible. This may 
include additional laboratory tests or investigations, histopathological examinations, or 
consultation with other health care professionals.
•
If a participant dies during participation in the study or during a recognized follow-up period, 
the investigator will provide UCB with a copy of any post-mortem findings including 
histopathology. 
•
New or updated information will be recorded in the originally completed CRF.
•
The investigator will submit any updated SAE data to UCB within 24 hours of receipt of the 
information.
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03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 142 of 220
Reporting of SAEs
SAE Reporting to UCB via an Electronic Data Collection Tool
•
The primary mechanism for reporting an SAE to UCB will be the electronic data collection 
tool.
•
If the electronic system is unavailable, then the site will use the paper SAE data collection tool 
(see next section) in order to report the event within 24 hours.
•
The site will enter the SAE data into the electronic system as soon as it becomes available.
•
After the study is completed at a given site, the electronic data collection tool will be taken 
off-line to prevent the entry of new data or changes to existing data.
•
If a site receives a report of a new SAE from a study participant or receives updated data on a 
previously reported SAE after the electronic data collection tool has been taken off-line, then 
the site can report this information on a paper SAE form (see next section) or to UCB by 
telephone.
•
Contacts for SAE reporting can be found in this protocol.
Reporting of SADEs
SADE Reporting to UCB 
NOTE: There are additional reporting obligations for medical device deficiencies that are potentially 
related to SAEs that must fulfil the legal responsibility to notify appropriate regulatory authorities and 
other entities about certain safety information relating to medical devices being used in clinical studies. 
•
Any device deficiency that is associated with an SAE must be reported to the sponsor within 
24 hours after the investigator determines that the event meets the definition of a device 
deficiency using the paper form provided by the sponsor.
•
The sponsor shall review all device deficiencies and determine and document in writing 
whether they could have led to an SAE. These shall be reported to the regulatory authorities 
and IRBs/IECs as required by national regulations.
•
Contacts for SAE reporting can be found in this protocol.
Reporting of AE and/or Device Deficiencies 
AE and/or Device Deficiencies Reporting to UCB 
NOTE: There are additional reporting obligations for medical device deficiencies that must fulfil the 
legal responsibility to notify appropriate regulatory authorities and other entities about certain safety 
information relating to medical devices being used in clinical studies. 
•
Any AE and/or device deficiencies must be reported to the Sponsor within 24 hours after the 
Investigator determines that the event meets the definition of a device deficiency using the 
paper form provided by the Sponsor.
•
The sponsor shall review all device deficiencies and determine and document in writing 
whether they meet device reporting requirement. 
•
Contacts for SAE reporting can be found in this protocol.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 143 of 220
10.9
Appendix 9: Abbreviations and trademarks
ADA
antidrug antibodies
ADE
adverse device effect
ADL
Activities of Daily Living
AE
adverse event
AESM
adverse event of special monitoring
ALP
alkaline phosphatase
ALT
alanine aminotransferase
app
application
AST
aspartate aminotransferase
BP
blood pressure
CDC
Centers for Disease Control and Prevention
CI
confidence interval
CIDP
chronic inflammatory demyelinating polyradiculoneuropathy
COVID-19
coronavirus disease 2019
CPM
Clinical Project Manager
CRF
Case Report Form
CRO
contract research organization
DCP
Data Cleaning Plan
DD
device deficiency
DNA
deoxyribonucleic acid
ECG
electrocardiogram
eCRF
electronic Case Report Form
EOS
End of Study
EQ-5D-5L
European Quality of Life Health Status Questionnaire-5 Dimensions, 
5 Levels
eqv
equivalent
EudraCT
European Union Drug Regulating Authorities Clinical Trials
EW
early withdrawal
FAS
Full Analysis Set
FcRn
neonatal Fc receptor
FIH
first-in-human
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 144 of 220
FSH
follicle stimulating hormone
GCP
Good Clinical Practice
GI
gastrointestinal
HBsAg
hepatitis B surface antigen
HIV
human immunodeficiency virus
HRQoL
Health-Related Quality of Life
HRT
hormone replacement therapy
IB
Investigator's Brochure
ICF
Informed Consent Form
ICH
International Council for Harmonisation
IDMC
Independent Data Monitoring Committee
IEC
Independent Ethics Committee
Ig
immunoglobulin 
IGRA
interferon-gamma release assay
IMP
investigational medicinal product
INR
International Normalized Ratio
IRB
Institutional Review Board
IRT
interactive response technology
ITP
primary immune thrombocytopenia
ITP-BAT
ITP–Bleeding Assessment Tool
ITP-PAQ
ITP-Patient Assessment Questionnaire
iv
intravenous
IVIg
intravenous immunoglobulin
K-PD
kinetic-pharmacodynamic
LLOQ
lower limit of quantification
LTB
latent tuberculosis
LTBI
latent tuberculosis infection
MG
myasthenia gravis
NTMBI
nontuberculous mycobacterial infection
OLE
open-label extension
OPSI
overwhelming post-splenectomy infection
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 145 of 220
PD
pharmacodynamic
PDILI
potential drug-induced liver injury
PD-PPS
Pharmacodynamic Per-Protocol Set
PEX
plasma exchange
PGI-C
Patient Global Impression of Change
PGI-S
Patient Global Impression of Severity
PK
pharmacokinetic
PK-PPS
Pharmacokinetic Per-Protocol Set
PPS
Per-Protocol Set
PRO
patient reported outcome
PS
Patient Safety
QMG
Quantitative MG 
QoL
quality of life
QTc
corrected QT interval
QW
once a week
Q2W
twice a week
RNA
ribonucleic acid
RO
receptor occupancy
SADE
serious adverse device effects
SAE
serious adverse event
SAP
Statistical Analysis Plan
sc
subcutaneous
SF-36
Short-Form 36-Item Health Survey
SFU
Safety Follow-Up
SMOG
Skin-mucosae-organs tool
SOP
standard operating procedure
SS
Safety Set
TB
tuberculosis
TEAE
treatment-emergent adverse event
TPO-RA
thrombopoietin-receptor agonist
ULN
upper limit of normal
PUBLIC COPY 
Y
val
C
val
OP
C
ek
B
ek
LIC
cleic aci
PUB
cleic aci
UB
r o
P
r o
PU
ument cannot be used to support any marketing authorization 
ati
ati
ati
at
riz
tho
au
g
eti
rk
m
ny
t a
po
upp
d
s
ccupancy
ed 
ccupancy
d t
adverse 
use
adverse 
se
ious adv
be 
ious adv
u
Statistic
ot b
Statistic
b
n
sub
n
sub
no
nn
an
t c
OG
m
OG
e
ocum
SOP
ocu
SOP
This docum
SS
do
SS
oc
s d
s d
s 
T
s d
s
plication and any extensions or variations thereof. 
f
eo
he
s t
on
iat
a
or
s
io
y
x
y
ns
device e
ex
device e
xt
erse even
ny 
erse even
y e
ical Analy
d a
ical Analy
an
bcutaneou
and
bcutaneou
nd
Short
on 
Short-F
a
i
Saf
io
Saf
io
ati
ca
applpl
ap


UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 146 of 220
US
United States
VAS
visual analog scale
WHO
World Health Organization
WOCBP
woman of childbearing potential
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
ati
ati
ati
application and any extensions or variations thereof. 


UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 147 of 220
10.10
Appendix 10: Rapid alert procedures
Not applicable.
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof. 


UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 148 of 220
10.11
Appendix 11: Karnofsky Performance Status Scale
Appendix removed. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof. 


UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 149 of 220
10.12
Appendix 12: ITP-BAT
Grading of bleeding symptoms at presentation and at each subsequent evaluation.1
Table 10-5:
ITP-Bleeding Assessment Tool
Type of bleeding
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE LAST VISIT2
0
1
2
3
4
SKIN
Petechiae (does not 
include steroid–induced 
or senile purpura)
No
Less than or equal to 
10 in a patient’s palm-
sized area3 in the most 
affected body area4
Any number if 
reported by the patient
More than 10 in a 
patient’s palm-sized area 
or more than 5 in at least 2 
patient’s palm-sized areas 
located in at least 2 
different body areas4, one 
above and one below the 
belt (in the most affected 
body areas) 4
More than 50, if 
scattered both above 
and below the belt
Ecchymoses
None or up to 2 in 
the same body area4, 
but smaller than a 
patient’s palm-sized 
area, if
a) spontaneous or b) 
disproportionate to 
trauma/constriction5
3 or more in the same 
body area4, but all 
smaller than a patient’s 
palm-sized area, if
a) spontaneous or 
b) disproportionate to 
trauma/constriction5
At least 2 in two 
different body areas4, 
smaller than a patient’s 
palm-sized area, if
a) spontaneous or 
b) disproportionate to 
trauma/constriction5
Any number and size 
if reported by the patient
From 1 to 5 larger than 
a patient’s palm-sized area, 
if
a) spontaneous or 
b) disproportionate to 
trauma/constriction5
with or without smaller 
ones
More than 5 
larger than a patient’s 
palm-sized area, if
a) spontaneous or 
b) disproportionate to 
trauma/ constriction5
BLIC COPY 
tient
CO
tient
ati
Y
ati
or mo
Y
or mo
patie
PY
patie
lo
P
lo
OP
PUBL
or more i
UB
or more i
dy area
PU
dy area4
U
4
U
aller t
P
aller t
BL
ot be used to support any marketing authorization 
a
AST VISI
ng 
AST VISI
a
3
tin
3
ing
eti
ke
0 in a
ma
0 in a
m
y
m-sized ar
y m
sized ar
han 5 in at
ny 
han 5 in at
t’s palm
any
t’s palm-
n
-si
y
si
ted in at le
t a
ted in at le
different bo
ort 
different bo
above
po
above an
an
belt (
pp
belt (
bo
p
bo
ar
up
the same
o s
the same
ut all
d to
ut all
an a patien
ed t
an a patien
zed area, i
sed
zed area, i
pontaneous
use
pontaneous
) dispropor
e u
) dispropor
trauma/co
be 
trauma/co
t b
A
b
A
dif
t
dif
u
su
This document cannot
cu
ot
u
ons or variations thereof. 
T
e
T2
e
2
of
re
the
ea 
ti
ea 
least 2
iati
least 2
zed areas
aria
zed areas
east 2
va
east 2
ody areas
r va
ody areas4
a
4
nd one belo
or 
nd one belo
in the mos
s o
in the mos
ody areas)
ns 
ody areas) 4
ons
M
s
M
sca
on
sca
s
on
nsion
sio
From
o
From
a pati
nsi
a pati
if
n
if
on
on and any exten
nt’s
te
nt’s
ifif
s or 
e
s or 
rtionate to 
y e
rtionate to 
onstriction
ny
onstriction
t least 2 in
d an
t least 2 in
fferent bod
nd a
fferent bod
smaller th
and
smaller th
palm
n an
palm-s
n
s
a) sp
n 
a) sp
b
n
b
application
pp
on
ns


UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 150 of 220
Type of bleeding
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE LAST VISIT2
0
1
2
3
4
Subcutaneous 
hematomas
No
1 smaller than a 
patient’s palm-sized area
Any number and size 
if reported by the patient
2 smaller than a 
patient’s palm-sized area, 
spontaneous 
2 smaller than a 
patient’s palm-sized area, 
disproportionate to trauma5
More than 2 
smaller or at least 1 
larger than a patient’s 
palm-sized area, 
spontaneous 
More than 2 
smaller or at least 1 
larger than a patient’s 
palm-sized area, 
disproportionate to 
trauma5
Bleeding from minor 
wounds6
No
Lasting <5 min
Any episode if 
reported by the patient
Lasting >5 min or 
interfering with daily 
activities
Requiring 
protracted medical 
observation at the 
time of this visit 
Medical report 
describing patient’s 
evaluation by a 
physician
MUCOSAL
Epistaxis7
No
Lasting <5 min
Any episode if 
reported by the patient
Lasting >5 min or 
interfering with daily 
activities
Packing or 
cauterization or 
in-hospital evaluation 
at the time of this 
visit 
Medical report 
describing packing or 
cauterization or in-
hospital evaluation
RBC transfusion 
or Hb drop >2g/dL
PUBLIC COPY 
OP
e if 
C
e if 
the patien
LIC 
the patien
OP
OP
OP
OP
used to support any marketing authorization 
a
za
or
ea, 
ke
ea, 
trauma
rke
trauma5
ke
5
More than 2
aut
More than 2
maller or 
au
maller or at
u
at
larger tha
ng 
larger tha
palm
ting
palm-
g
-s
g
s
spo
ti
spo
th
eti
o
Lasting 
ort 
Lasting 
interferin
por
interferin
activit
pp
activit
t a
up
se
ot be u
be
Lastin
be 
Lastin
t b
An
b
An
rep
t 
rep
u
This document cannot
m
ot
y extensions or variations thereof. 
least 1
of.
least 1
an a patient
reo
an a patient
sized area, 
ere
sized area, 
ntaneous 
the
ntaneous 
s
More th
s th
More th
smaller 
ns 
smaller 
large
on
large
pa
o
pa
on
>5 min or 
r va
>5 min or 
ng with da
or 
ng with da
ties
s
ties
va
ns
xt
on and any e
ng <5 min
ny 
ng <5 min
ny episode
d an
ny episode
ported by th
d a
ported by th
y e
application
lic
on


UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 151 of 220
Type of bleeding
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE LAST VISIT2
0
1
2
3
4
Oral cavity – gum 
bleeding7
No 
Lasting <5 min
Any episode if 
reported by the patient
Lasting >5 min or 
interfering with daily 
activities
Requiring 
protracted medical 
observation at the 
time of this visit 
Medical report 
describing patient’s 
evaluation by a 
physician
Oral cavity –
hemorrhagic bullae or 
blisters
No
Less than 3
Any number if 
reported by the patient
From 3 to 10 but no 
difficulty with mastication
More than 10 or 
more than 5 if 
difficulty with 
mastication
Oral cavity - bleeding 
from bites to lips & 
tongue or after 
deciduous teeth loss
No
Lasting <5 min
Any episode if 
reported by the patient
Lasting >5 min or 
interfering with daily 
activities
Interventions to 
ensure hemostasis or 
in-hospital evaluation 
at the time of this 
visit
Medical report 
describing 
interventions to 
ensure hemostasis or 
in-hospital evaluation
Subconjunctival 
hemorrhage 
(not due to conjunctival 
disease)
No
Petechiae/ 
hemorrhage partially 
involving one eye
Any episode if 
reported by the patient
Petechiae/ hemorrhage 
partially involving both 
eyes, or diffuse 
hemorrhage in one eye
Diffuse 
hemorrhage in both 
eyes
ORGAN (and internal 
mucosae)
PUBLIC COPY 
nt
CO
nt
Y
Fr
Y
Fr
diffic
PY
diffic
OP
min
C
min
sode if 
LIC
sode if 
d by the p
BL
d by the p
C
ument cannot be used to support any marketing authorization 
a
za
or
Requiring 
aut
Requiring 
otracted m
g au
otracted m
observatio
ng 
observatio
time of
ting
time of
ti
d
th
eti
3 to 10 but
ny 
3 to 10 but
lty with ma
any
lty with ma
m
tient
s
tient
ppo
Las
po
Las
inter
pp
inter
a
p
a
o
t
up
t b
P
h
This docum
t b
ot
um
doc
o
any extensions or variations thereof. 
medical 
of
medical 
on at the
eo
on at the
f this visit 
ere
f this visit 
Medical r
the
Medical r
describing
s th
describing
evaluati
ns 
evaluati
phys
on
phys
on
no
at
no
astication
aria
astication
o
tio
sting >5 mi
or
sting >5 mi
rfering wit
ns o
rfering wit
ctivities
ons
ctivities
r
ns
on and an
Petechiae/ 
d a
Petechiae/ 
hemorrhage
nd 
hemorrhage
involving
an
involving
n a
A
a
A
re
n
re
application
an
on
pli
a


UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 152 of 220
Type of bleeding
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE LAST VISIT2
0
1
2
3
4
Gastrointestinal 
bleeding not explained 
by visible mucosal 
bleeding or lesion:
Hematemesis,
Melena,
Hematochezia,
Rectorrhagia
No
Any episode if 
reported by the patient
Present at the visit
Described in a medical 
report
Requiring 
endoscopy8 or other 
therapeutic 
procedures or in-
hospital evaluation at 
the time of this visit
Medical report 
prescribing 
endoscopy8 or other 
therapeutic 
procedures or in-
hospital evaluation
RBC transfusion 
or Hb drop >2g/dL
Lung bleeding
Hemoptysis
Tracheobronchial 
bleeding
No
Any episode if 
reported by the patient
Present at this visit
Described in a medical 
report
Requiring 
bronchoscopy8 or 
other therapeutic 
procedures or in-
hospital evaluation at 
the time of this visit
An equivalent 
episode if described 
in a medical report
RBC transfusion 
or Hb drop >2g/dL
Hematuria
No
Any episode if 
reported by the patient
Microscopic (lab 
analysis)
Macroscopic 
Described in a medical 
report
Macroscopic, and 
requiring cystoscopy8
or other therapeutic 
procedures or in-
hospital evaluation at 
the time of this visit
RBC transfusion 
or Hb drop >2g/dL
COPY 
OP
PUBLIC CO
if 
C
if 
he patient
IC 
he patient
CO
ort any marketing authorization 
a
za
or
Requiring 
aut
Requiring 
ndoscopy
g au
ndoscopy8
u
8
u
therapeuti
ng 
therapeuti
proced
ting
proced
hosp
ti
hosp
thth
th
eti
upport
po
Prese
por
Prese
pp
D
p
D
re
p
re
annot be used to sup ort
ot
up
ocument can
an
This doc
s doc
variations thereof. 
or other 
of.
or other 
ic
r
ic
dures or in
ere
dures or in
pital evalu
the
pital evalu
he time of 
th
he time of 
ns
Med
s 
Med
presc
on
presc
en
o
en
on
nsions or v
nt at this v
or 
nt at this v
escribed in
s o
escribed in
port
on
port
application and any exten
v
ns
n a
A
a
A
re
n
re
a
on


UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 153 of 220
Type of bleeding
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE LAST VISIT2
0
1
2
3
4
An equivalent 
episode if described 
in a medical report
Menorrhagia
(compared to pre-ITP 
or to a phase of disease 
with normal platelet 
count)9
No
Doubling number. of 
pads or tampons in last 
cycle compared to pre-
ITP or to a phase of 
disease with normal 
platelet count
Score >100 using 
PBAC in the last cycle, if 
normal score in pre-ITP 
cycles or in a phase of 
disease with normal 
platelet count
Changing pads more 
frequently than every 
2 hrs. or clot and flooding
Requiring combined 
treatment with 
antifibrinolytics and 
hormonal therapy or 
gynecological 
investigation (either at this 
visit or described in a 
medical report)
Acute 
menorrhagia 
requiring hospital 
admission or 
endometrial ablation 
(either at this visit or 
described in a 
medical report)
RBC transfusion 
or Hb drop >2g/dL
Intramuscular 
hematomas
(only if diagnosed by a 
physician with an 
objective method)
No
Post trauma, 
diagnosed at this visit, if 
judged disproportionate 
to trauma
An equivalent 
episode if described in a 
medical report
Spontaneous, 
diagnosed at this visit 
An equivalent episode 
if described in a medical 
report
Spontaneous or 
post trauma (if 
judged 
disproportionate to 
trauma) diagnosed at 
this visit and 
requiring hospital 
admission or surgical 
intervention
An equivalent 
episode if described 
in a medical report
RBC transfusion 
or Hb drop >2g/dL
Hemarthrosis
No
Post trauma, 
diagnosed at this visit, 
Spontaneous, 
diagnosed at this visit, 
Spontaneous or 
post trauma (if 
Spontaneous or 
post trauma (if 
OPY
C
Y
C
freque
PY 
freque
2
P
2 h
P
h
PUBLIC COP
C
mal
C C
mal
>100 usin
BLIC
>100 usin
in the las
UBL
in the las
mal score 
PUB
mal score 
cles or in
PU
cles or in
ase
P
ase
OP
marketing authorization 
a
za
or
n equivalen
auth
n equivalen
isode if des
au
isode if des
in a medic
ng a
in a medic
th
eti
upport any m
ing pads m
ny m
ing pads m
ntly tha
any
ntly than ev
ny
n ev
s. or clot an
t an
s. or clot an
o
Requirin
ort 
Requirin
treatmen
por
treatmen
antifib
pp
antifib
hor
p
hor
used to sup
g
s
g
cycle, if 
su
cycle, if 
n pre
to
n pre-
to
-ITP
o s
ITP
a phase of 
d to
a phase of 
ith normal
ed 
ith normal
et count
se
et count
m
up
ot be us
e
Post trau
e u
Post trau
diagnosed
be 
diagnosed
judged
t be
judged
to t
t 
to t
s document cannot
us
oc
ot
oc
This oc
oc
oc
s
oc
nsions or variations thereof. 
nt 
f
nt 
scribe
of
scribed 
f.
d 
cal report
eof
cal report
on
more 
at
more 
very
ri
very
nd flooding
vari
nd flooding
ng combin
r va
ng combin
t with
or
t with
brinolytics
s o
brinolytics
rmonal the
ns 
rmonal the
gynecolog
ion
gynecolog
investig
sio
investig
visit
ns
visit
m
n
m
extensions or variatio
e
l
oio
ns
o
on and any ex
uma, 
y
uma, 
d at this vi
ny 
d at this vi
d dispropor
any
d dispropor
rauma
d a
rauma
a
An equ
and
An equ
episode
n an
episode
med
n 
med
application
ex
on
ap
No
a
No
ap


UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 154 of 220
Type of bleeding
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE LAST VISIT2
0
1
2
3
4
(only if diagnosed by a 
physician with an 
objective method)
function conserved or 
minimally impaired, if 
judged disproportionate 
to trauma
An equivalent 
episode if described in a 
medical report
function conserved or 
minimally impaired
An equivalent episode 
if described in a medical 
report
judged 
disproportionate to 
trauma), diagnosed at 
this visit and 
requiring 
immobilization or 
joint aspiration
An equivalent 
episode if described 
in a medical report
judged 
disproportionate to 
trauma) diagnosed at 
this visit and 
requiring surgical 
intervention
An equivalent 
episode if described 
in a medical report
Ocular bleeding
(only if diagnosed by a 
physician with an 
objective method)
No
Any post trauma 
vitreous or retinal 
hemorrhage involving one 
or both eyes with or 
without impaired/blurred 
vision present at this visit 
if judged disproportionate 
to trauma
An equivalent episode 
if described in a medical 
report
Spontaneous 
vitreous or retinal 
hemorrhage 
involving one or both 
eyes with 
impaired/blurred 
vision present at this 
visit
An equivalent 
episode if described 
in a medical report
Spontaneous 
vitreous or retinal 
hemorrhage with loss 
of vision in one or 
both eyes present at 
this visit
An equivalent 
episode if described 
in a medical report 
Intracranial 
bleeding10:
intracerebral, 
intraventricular, 
subarachnoidal, subdural, 
extradural
(only if diagnosed with 
an objective method at 
the visit or described in 
a medical report 
provided by the 
patient)
No
Any post trauma event 
requiring hospitalization
Any spontaneous 
event requiring 
hospitalization in 
presence of an 
underlying 
intracranial lesion
Any spontaneous 
event requiring 
hospitalization 
without an 
underlying 
intracranial lesion
PUBLIC COPY 
P
OPY
PY
PY
OP
ny marketing authorization 
a
za
or
d 
a
d 
proportion
au
proportion
trauma), d
ng a
trauma), d
this visi
ting
this visi
requ
tin
requ
im
im
th
eti
upport any
Any post tra
t an
Any post tra
treous or r
rt a
treous or r
hemorrha
por
hemorrha
or both
ppo
or both
with
pp
with
p
ot be used to sup
any
up
u
This document cannot
doc
o
ot
riations thereof. 
nate to 
of
nate to 
diagnosed a
eof
diagnosed a
t and
ere
t and
iring
he
iring
mmobilizat
the
mmobilizat
joint aspi
s t
joint aspi
ons
A
s
A
ep
o
ep
on
nsions or varia
auma
vari
auma
etinal 
va
etinal 
age involvi
or v
age involvi
h eyes with
s or
h eyes with
hout impai
ns 
hout impai
vision pres
ons
vision pres
if judged
sio
if judged
to tra
ns
to tra
n
on and any exten
ria
ns
y e
application
a
on


UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 155 of 220
Type of bleeding
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE LAST VISIT2
0
1
2
3
4
Other internal 
bleeding:
hemoperitoneum
hemopericardium
hemothorax 
retroperitoneal bleeding
hepatic and splenic 
peliosis with organ 
rupture
retroorbital bleeding
metrorrhagia
etc.
(only if diagnosed with 
an objective method at 
the visit or described in 
a medical report 
provided by the 
patient)
No
Any event 
requiring 
hospitalization 
<48 hrs.
Any event 
requiring 
hospitalization 
>48 hrs. or RBC 
transfusion or Hb 
drop >2g/dL
Hb=hemoglobin; hrs=hours; ITP=immune thrombocytopenia; PBAC=Pictorial Blood Assessment Chart; RBC=red blood cell; SMOG=Skin-Visible Mucosa-
Internal Organs tool
1 In case of study participants examined for the first time, all types of bleeding occurring at the visit and in the 15 days preceding the visit should be considered. 
2 Each type of bleeding should be graded based on the worst bleeding manifestation that occurred during each observation period or in the 15 days preceding the 
first visit.
3 Study participant’s own palm size is commonly considered to be proportional to body surface area. Palm=the inner surface of the hand stretching between the 
distal crease of the wrist and the bases of the fingers (fingers surface excluded).
4 Body areas include: face, neck, right and left upper limbs (considered separately), right and left lower limbs (considered separately), trunk, abdomen, and 
recumbent areas (for the ambulatory patient means the area below the knees). 
5 Bleedings considered proportionate to trauma/constriction on a clinical ground should not be reported for skin domain.
6 Minor wound means superficial skin cuts (eg, by shaving razor, knife, or scissors).
7 Epistaxis and gum bleeding are also reported in some normal study participants. Thus, a critical judgment is required in grading these manifestations; they 
should be reported only if judged more severe when compared with pre-ITP bleeding, if any.
PUBLIC COPY 
OP
cannot be used to support any marketing authorization 
a
za
or
Any event 
aut
Any event 
quiring
g au
quiring
hospitaliz
ng 
hospitaliz
<48
ting
<48 hr
g
hr
th
up
eti
be
cytopenia; 
t be
cytopenia; 
e first time
nno
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8 Any endoscopic investigations should be considered for grading only if performed for therapeutic purpose and not solely for diagnostic purpose.
9 In girls at menarche, grade 1 cannot be assigned, lacking comparison with previous cycles.
10 Intracranial bleeding should always be reported, irrespective of its grade. For example, if a woman had S2 (subcutaneous hematoma) M2 (epistaxis) O3 
(menorrhagia) and an intracranial bleeding grade 2 (post trauma, requiring hospitalization), the SMOG index is S2M2O3 (intracranial 2). If the same 
participant also had intracranial bleeding grade 3, the SMOG index is S2M2O3 (intracranial 3) (see text).
Note: Grading is based on physical examination at the time of the visit by the physician or expert nurse or on study participant’s history supplemented by 
available medical reports. Bleeding manifestations reported by the study participant but not visible at the time of data collection are graded 1. Grade 5 is 
assigned to fatal bleeding.
Note: Illustrative examples are available on the website of the Hematology Project Foundation (http://itpbat.fondazioneematologia.it/).
Note: To receive a grade >1, all non-overt skin and non-overt mucosal bleeding (petechiae, ecchymoses, subcutaneous hematomas, vesicles/bullae 
subconjunctival bleeding) should be visible at the time of visit for grading by the physician or expert nurse taking the history. 
Note: For bleeding from minor wounds and overt-mucosal bleeding (epistaxis, gum, bleeding from bites to lips & tongue or after deciduous teeth loss/extraction) 
and all organ bleeding, a medical record describing the symptom or indicating a specific intervention/prescription should be also taken into account for grading.
Note: Requirement for ITP-specific treatments and anti-fibrinolytics (apart from menorrhagia) was not considered for grading, due to their subjective nature and 
their adoption not only to control actual bleeding but also to reduce the “risk” of impendent or future bleeding.
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rization 
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This document cannot be used to support any
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rization 
horiz
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ation 
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This d
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application and any extensions or variations thereof. 
and any extensions or variations thereof


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rization 
thoriz
This d
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application and any extensions or variations thereof
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tensions or variations there


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PUB
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application and any extensions or variations thereof. 
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ization 
authoriz
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application and any extensions or variations thereof.
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orization 
hor
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s document cannot be used to support any marketing autho
of. 
application and any extensions or variations thereof
y e
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orization 
uthori
This d
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be
be used to support any marketing auth
of. 
application and any extensions or variations thereof
ny
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ization 
authoriz
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s document cannot be
be 
be used to support any marketing au
. 
application and any extensions or variations thereof.
ny
ny extensions or variations the


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et
eting authorizati
application and any extensions or variations the
he
hereof. 


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ment cannot be used to support any marketing authorizatio
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pplication and any extensions or variations thereof. 


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10.17
Appendix 17: PGI-S
The following question asks you about your current overall symptoms.
Please check the box that best describes your current situation.
How would you describe your ITP symptoms during the past week?
None
Mild
Moderate
Severe
Very severe
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10.18
Appendix 18: PGI-C
The following question asks you about your overall symptoms now compared to before starting 
treatment within this clinical study. Please check the box that best describes your current
situation.
How would you describe your current ITP symptoms compared to before you started 
treatment in this clinical study?
Very much worse
Much worse
A little bit worse
No change
A little bit improved
Much improved
Very much improved
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ereof. 


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10.21
Appendix 21: Sampson Criteria Questionnaire
Anaphylaxis is highly likely when any of the following 3 criteria is fulfilled 
(Sampson et al, 2006):
1. Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal 
tissue, or both (eg, generalized hives, pruritus or flushing, swollen lips-tongue-uvula)
AND AT LEAST ONE OF THE FOLLOWING
c.
Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced peak 
expiratory flow [PEF], hypoxemia)
d. Reduced BP or associated symptoms of end-organ dysfunction (eg, hypotonia [collapse], 
syncope, incontinence)
2. Two or more of the following that occur rapidly after exposure to a likely allergen for that 
patient (minutes to several hours):
a.
Involvement of the skin-mucosal tissue (eg, generalized hives, itch-flush, swollen 
lips-tongue-uvula)
b.
Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF, 
hypoxemia)
c.
Reduced BP or associated symptoms (eg, hypotonia [collapse], syncope, 
incontinence)
d.
Persistent GI symptoms (eg, crampy abdominal pain, vomiting)
Reduced blood pressure after exposure to known allergen for that study participant (minutes to 
several hours): Systolic BP of less than 90mmHg or greater than 30% decrease from the study 
participant’s Baseline systolic BP value.
PUBLIC COPY 
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10.22
Appendix 22: Management of headaches
Based on current available clinical data, headache is the most commonly reported adverse drug 
reaction in study participants treated with rozanolixizumab. Study participants should be well 
informed of this potential adverse drug reaction and should be instructed on how to manage it.
Determination of the severity of headache will be consistent with National Cancer Institute 
Terminology Criteria for Adverse Events (CTCAE) version 5.0. Severe headache is defined as 
severe pain limiting self-care activity of daily living (ADL). Self-care ADL refers to bathing, 
dressing and undressing, feeding self, using the toilet, and taking medications. 
In the event of a headache the investigators should take the medical history of previous 
headaches, concomitant medication, and comorbidities (eg, asthma) into consideration.
Study participants experiencing a moderate, severe and/or serious headache will complete the 
Headache Questionnaire (Appendix 20, Section 10.20) daily until resolution (eg, the headache 
becomes nonserious, mild, or is completely resolved, whichever comes first). If the severe and/or 
serious headache is initially reported at a home visit or during a telephone call, the study 
participant should be evaluated by a healthcare professional at the study site as soon as possible 
for further investigations. Study participants should be monitored for signs and symptoms 
suggestive of central nervous system involvement and evaluated immediately if other causes (eg, 
meningitis, intracranial bleeding) are suspected. Further neurological workup may be performed 
(if indicated) at the discretion of the investigator or the treating physician and may include a 
computed tomography scan, magnetic resonance imaging and/or a lumbar puncture for cerebral 
spinal fluid collection. In addition, samples for exploratory safety biomarkers should be collected 
for study participants experiencing severe headache or serious headache when possible. These 
investigations will be performed to further understand the mechanism of headaches in the study 
participants.
Treatment must be permanently discontinued if a study participant has a serious headache that is 
considered related to the IMP in the opinion of the investigator. If a study participant experiences 
a severe AE of headache that is considered related to the IMP in the opinion of the investigator, 
the dose of IMP may be reduced or the treatment may be temporarily put on hold. If deemed 
appropriate by the investigator and agreed upon by the study participant and the sponsor, the 
study treatment can resume upon the resolution of the severe headache event, at the previous 
dose or at a lower dose. The benefit and risk of the treatment should be carefully considered prior 
to reinitiating the IMP. If a study participant experiences a second episode of treatment related 
severe headache in the opinion of the investigator, the treatment can only be continued upon 
agreement with the sponsor, investigator, and study participant taking benefit and risk into 
consideration. If the benefit-risk balance is not acceptable, then the participant must discontinue 
the IMP. If a participant experiences >2 severe headaches that are considered related to the IMP 
in the opinion of the investigator, the treatment must be permanently discontinued. 
Dosing modifications are allowed if judged necessary by the investigator from 
 
 based on specific volume reduction per protocol guidance, 
provided the treatment is effective as evidenced by relevant efficacy measurements (eg, platelet 
count ≥30×109/L). 
Headaches will be treated as clinically indicated according to national guidelines. It is 
recommended that the study participant has an analgesic available in case of headache with the 
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03 Dec 2021
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Page 185 of 220
instruction for frequency and dosage provided by a health care professional. The analgesic can 
be started at the early onset of headache. Study participants experiencing any treatment related 
headache will be followed until resolution of the event.
Prophylactic treatment of headaches may be permitted for study participants who have 
experienced previous episodes of treatment related moderate or severe headache after discussion 
with the medical monitor. The benefit risk of continuing treatment with IMP and chronic 
prophylactic treatment with analgesics must be carefully evaluated by the investigator.
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on
ti
on
application and any extensions or variations thereof. 


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Page 186 of 220
10.23
Appendix 23: Management of diarrhea
Severe (Grade 3) diarrhea is defined as an increase of ≥7 stools per day or hospitalization for 
management of diarrhea or limiting self-care ADL. Determination of the severity of diarrhea will 
be consistent with CTCAE version 5.0 (see Appendix 3, Section 10.3).
Diarrhea will be treated as clinically indicated according to the local guidelines.
Stool samples may be collected for stool analysis to rule out infection for study participants 
reporting severe diarrhea. Stool sampling will be done as clinically indicated in the opinion of 
the investigator and assessed per local guidance. In addition, collection of blood samples for 
assessment of exploratory safety biomarkers is required for study participants with severe GI 
disturbances including diarrhea. 
In study participants experiencing severe treatment related diarrhea, dosing modifications are 
allowed, if judged necessary by the investigator, from 
 based on specific volume reduction per protocol guidance, provided the treatment is 
effective as evidenced by relevant efficacy measurements (eg, platelet count ≥30×109/L).
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03 Dec 2021
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Confidential
Page 187 of 220
10.24
Appendix 24: Management of infusion reactions or 
hypersensitivity reactions
Study participants must be closely monitored for reactions during and after the IMP 
administration period. Standard precautions must be taken for the study participants with regard 
to potential infusion related reactions. Suggested management guidelines for infusion-related 
reactions and anaphylaxis at the study site are provided in Table 10-7. Definitions of the severity 
of the relevant events will be consistent with CTCAE version 5.0 (see Appendix 3, Section 10.3). 
Fully trained healthcare professionals administering the IMP at home should follow their own 
management guidelines, which should be reviewed and endorsed by the investigator prior to first 
home administration.
Table 10-7: Suggested management guidelines at the study site for infusion 
reactions
Type of reaction
Suggested action
Acute – Mild
Grade 1
Monitor vital signs every 10 min.
If the reaction worsens to Grade 2, follow the instructions below.
Acute – Moderate
Grade 2
Interrupt/hold infusion temporarily to further assess and initiate 
treatment if necessary. 
Consider the use of iv fluid and antihistamine iv or im.
Consider administering paracetamol or NSAIDs.
Monitor vital signs initially every 5 min.
If the reaction improves and upon further assessment it is clear that the 
event is not an anaphylaxis, restart the infusion cautiously. Continue to 
monitor vital signs every 5 minutes.
If reaction recurs or worsens to Grade 3, discontinue infusion.
Acute – Severe
Grade 3 or 
anaphylaxis
Discontinue IMP infusion permanently.
Alert crash team.
Maintain airway; ensure oxygen is available.
Administer:
−
Antihistamine iv/im, corticosteroids iv, epinephrine im, and iv 
fluids as appropriate.
−
Monitor vital signs every 2 min.
−
Hospitalize, if condition not improving or worsens.
−
Monitor study participant until symptoms resolve.
CTCAE=Common Terminology Criteria for Adverse Events; im=intramuscular; IMP=investigational medicinal 
product; iv=intravenous(ly); NSAID=nonsteroidal anti-inflammatory drug
Note: Management criteria were adapted from the CTCAE v5.0 (National Cancer Institute, 2017).
In case of suspected anaphylaxis, the Sampson’s Criteria (Sampson et al, 2006) should be 
accessed and Appendix 21 (Section 10.21, Sampson Criteria Questionnaire) should be 
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03 Dec 2021
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Page 188 of 220
completed. The infusion must be discontinued immediately, and emergency resuscitation 
measures implemented.
In study participants experiencing an infusion-related reaction or anaphylaxis, blood samples will 
be collected as soon as possible, while the event is ongoing, to investigate the nature of the 
reaction as per Schedule of Activities (Section 1.3).
Samples for serum complement (C3, C4) and plasma complement (C3a, C5a) should be 
collected as specified in the Schedule of Activities (Section 1.3). Additional tests such as IgE 
levels, tryptase may be performed when there is a suspicion of Type I or III hypersensitivity 
reaction. The results of all monitoring, including laboratory testing, should be made available to 
the study site and Sponsor.
PUBLIC COPY 
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nsitivity 
This document cannot be used to support any marketing au
de availab
uth
de availab
application and any extensions or variations thereof. 
ab


UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 189 of 220
10.25
Appendix 25: Management of infections and 
hypogammaglobulinemia
Study participants who have the signs or symptoms of any infection should be monitored closely 
and managed according to local guidelines. This may include tests for specific organisms if 
clinically indicated.
If a study participant has a significant infective episode including but not limited 
to bacteremia/sepsis, infectious meningitis, septic arthritis, osteomyelitis, complicated 
pneumonia, or visceral abscess which may or may not result in hospitalization, they MUST 
discontinue IMP, perform the EW Visit, enter the SFU Period and complete the EOS Visit. This 
list is not intended to be all inclusive and the investigator is expected to apply his/her judgment 
on continuing IMP based on the clinical situation at hand.
To maintain the study integrity, study site personnel, the UCB and CRO study teams will remain 
blinded to IgG levels. However, to ensure study participants’ safety, serum IgG level will be 
monitored by unblinded Medical Monitors external to UCB. In case the serum IgG level 
decreases <1g/L, as described below and in Table 10-8, the unblinded Medical Monitors will 
inform the investigator. 
The most recently available IgG value is the trigger for discussions between the unblinded 
Medical Monitors and the investigator and for any decisions on changing the dose of IMP/ 
triggering a mock infusion. All discussions and decisions related to the benefit-risk of dose 
changes/mock infusions are to be based on a holistic approach of the study participant’s status, 
including platelet response (eg, study participant’s ITP history, stability of the current response, 
past and current platelet values), current signs and symptoms of non-serious/serious infection, 
potential risk of acquiring a non-serious/serious infection in the foreseeable future and are at the 
sole discretion of the investigator. 
The investigator must document the respective benefit-risk assessments and decisions in the 
study participant’s source documents. 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 190 of 220
Table 10-8: Management of infections and hypogammaglobulinemia
IgG value
Actions 
Outcome
IgG <1g/La
Unblinded medical monitor 
informs the investigator
Investigator decides to 
eitherb:
•
maintain the dose
•
reduce the dose
•
request for a mock 
infusion to be triggered
based on the study 
participant’s status regarding 
platelets response, signs and
symptoms of non-
serious/serious infection, 
potential risk of acquiring a 
non-serious/serious infection
AE=adverse event; eCRF=electronic case report form; IXRS= Interactive Voice/Web Response System
a Events of hypogammaglobulinemia must not be captured as an AE in the eCRF, to protect the blind. 
b In the IXRS, the investigator can only reduce the dose, while the unblinded Medical Monitors can only trigger the 
mock infusion.
Dose adjustments/mock infusions
The dose of IMP can be reduced from 
 as needed. 
The IgG would be expected to return to values ≥1g/L in up to 3 to 4 weeks (after a dose 
decrease/mock infusion is triggered). The level of IgG recovery will depend on the IgG observed 
value that triggered the intervention and the intra-study participants variability, so that the IgG 
level may not immediately increase, and a delayed effect could be expected. 
The study participant will need to be reassessed on an ongoing basis regarding platelet response 
and risk of infection until the serum IgG returns to values ≥1g/L. The dose may be further 
decreased, or a mock infusion triggered, if needed.
In case a mock infusion is triggered, IMP administration may be restarted at a lower dose 
compared to the previous dose in order to decrease the likelihood of any further repeated 
reduction in the IgG level <1g/L. 
Ad hoc assessments (eg, additional weekly IgG samples) may be performed to monitor recovery 
of IgG levels. 
Splenectomized study participants
Splenectomized study participants are at a higher risk of infections, especially of OPSI. 
Irrespective of the IgG level, in case a splenectomized study participant develops a (persistent or 
recurring) nonserious infection, the dose of IMP can be reduced, or the IMP treatment may be 
temporarily stopped, when appropriate, at the investigator’s discretion. The IMP treatment may 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 191 of 220
be resumed at the previous dose after the resolution of the event. The investigator may also reach 
out to the unblinded Medical Monitors, as needed. 
Local guidelines regarding antibiotic prophylaxis in splenectomized study participants should be 
followed. Splenectomized study participants should have a prophylactic antibiotic available, 
unless they are already taking an antibiotic as per local guidance. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof. 


UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 192 of 220
10.26
Appendix 26: Protocol Amendment History
The protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the Table of Contents.
Amendment 2 (29 Sep 2020)
Overall Rationale for the Amendment
The primary reason for this protocol amendment was to incorporate changes in the endpoints, the 
statistical analysis section and to incorporate agency required local protocol amendments into 
one global protocol.
Additional updates were incorporated to provide further clarity on the protocol or to correct 
errors.
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union.
Section # and Name
Description of Change
Brief Rationale
Global
Minor administrative, consistency, 
formatting and typographical 
changes have been made.
Updated to provide clarity and be 
consistent with remainder of 
protocol.
Global
Where applicable, rozanolixizumab 
has been replaced with 
investigational medicinal product 
(IMP).
Updated to ensure placebo is 
included in the context of the 
applicable section.
Global
The list of the secondary efficacy 
endpoints has been reordered.
Updated to match the sequence of 
analysis.
Global 
Where applicable, the wording 
“4-week” was removed from “the 
4-week Screening Period”.
Wording updated for consistency 
reasons.
Global
“Prednisolone” changed to 
“prednisone”.
Updated to UCB standards.
Global
All reference to the Fisher’s Exact 
test has been removed from the 
primary analysis and included as a 
separate supplemental estimand. 
For the primary analysis more 
details regarding the 
Cochran-Mantel-Haenszel test 
have been added.
To provide a more accurate 
description of the analysis and to 
address FDA statistical comments 
on confirmatory analyses.
Global
Japan specific regulations have 
been highlighted throughout the 
protocol and added to Appendix 8, 
Section 10.8.
In accordance with local 
regulations and actual condition of 
medical treatment in Japan.
Serious adverse event 
reporting 
For participants in Japan only: 
Additional reporting instructions 
for SAE reporting (investigational 
In accordance with local 
regulations in Japan. The infusion 
syringe driver and infusion set 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 193 of 220
Section # and Name
Description of Change
Brief Rationale
device) and device deficiency 
reporting specific for Japan have 
been included.
supplied by the sponsor are not 
approved in Japan.a
1.1 Synopsis, Rationale
1.1 Synopsis, Overall 
design
2.1 Study rationale
The study criteria have been 
modified to include study 
participants who have failed or 
were intolerant to two or more 
prior ITP therapies.
Global implementation of an 
ANSM request and implement 
feedback received from the FDA.
1.1 Synopsis, Objectives 
and endpoints
3 Objectives and endpoints
The primary efficacy endpoint has 
been updated to delete “as defined 
by proportion of study participants 
who have platelet responses”.
Updated to be consistent with UCB 
writing conventions.
1.1 Synopsis, Objectives 
and endpoints
3 Objectives and endpoints
The secondary efficacy endpoint 
has been updated from 
“Cumulative number of visits” to 
“Cumulative number of weeks” 
and "over the 24-week treatment 
period" was added.
Updated to provide clarity.
1.1 Synopsis, Objectives 
and endpoints
3 Objectives and endpoints
The secondary efficacy endpoint 
“Time to first Clinically 
Meaningful Platelet Response of 
≥50x109/L: time from starting 
treatment to achievement of first 
response of ≥50x109/L” was 
updated to include “first”.
Updated for consistency within the 
description of this endpoint.
1.1 Synopsis, Objectives 
and endpoints
3 Objectives and endpoints
The secondary efficacy endpoint 
“Complete Response defined as 
platelet count ≥100x109/L 
confirmed on at least 2 separate 
occasions at two adjacent nominal 
visits at least 7 days apart, and 
absence of bleeding by visit” has 
been moved to “other efficacy 
endpoints”.
Endpoint did not measure different 
manifestation of the disease and 
did provide redundant information 
with another key secondary 
endpoint.
1.1 Synopsis, Objectives 
and endpoints
3 Objectives and endpoints
The secondary efficacy endpoint 
related to the ITP Patient 
Assessment Questionnaire 
(ITP-PAQ) Symptoms Score has 
been modified.
Corrected to clarify the variable.
1.1 Synopsis, Objectives 
and endpoints
3 Objectives and endpoints
The other efficacy endpoint 
relating to “Duration of Clinically 
Meaningful Platelet Response” has 
been updated.
Updated to clarify it is the first 
response.
1.1 Synopsis, Objectives 
and endpoints
The other efficacy endpoint “Time 
to first Complete Response: time 
Endpoint did not measure different 
manifestation of the disease and 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 194 of 220
Section # and Name
Description of Change
Brief Rationale
3 Objectives and endpoints
from starting treatment to 
achievement of Complete 
Response” has been deleted.
did provide redundant information 
with another key secondary 
endpoint.
1.1 Synopsis, Objectives 
and endpoints
3 Objectives and endpoints
The other efficacy endpoint 
“Duration of first Complete 
Response: measured from 
achievement of Complete 
Response to loss of Complete 
Response (loss of Complete 
Response defined as platelet count 
<100x109/L or bleeding. Platelet 
counts confirmed on at least 2 
separate occasions)” has been 
deleted.
The secondary efficacy endpoint on 
"Complete Response" was deleted 
as it did not measure a different 
manifestation of the disease. For 
consistency, the "Duration of 
Complete Response" was deleted 
too.
1.1 Synopsis, Objectives 
and endpoints
3 Objectives and endpoints
The following text has been added 
to the other efficacy endpoint 
“Usage of rescue therapy by visit”.
To clarify the timepoint of 
measuring the endpoint.
1.1 Synopsis, Objectives 
and endpoints
3 Objectives and endpoints
Additional “other” efficacy 
endpoints have been added:
• Cumulative number of weeks 
over the planned 24-week 
treatment period with platelet count 
of ≥100x109/L.
• Cumulative number of weeks 
over the planned 24-week 
treatment period with platelet 
counts ≥30×109/L and at least 
doubling from Baseline.
• Mean change from Baseline in 
platelet count by visit.
• Clinically Meaningful Platelet 
Response of ≥50x109/L, for at least 
4 out of 6 weeks during the last 
6 weeks (Week 19 to 25).
• Clinically Meaningful Platelet 
Response of ≥50x109/L, for at least 
6 out of 8 weeks during the last 
8 weeks (Week 17 to 25).
Updated to include missing details.
1.1 Synopsis, Objectives 
and endpoints
3 Objectives and endpoints
The following text has been added 
to the safety endpoint:
Occurrence of TEAEs leading to 
withdrawal of investigational 
medicinal product (IMP) (ie, study 
discontinuation)
Updated to provide clarity.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 195 of 220
Section # and Name
Description of Change
Brief Rationale
1.1 Synopsis, Objectives 
and endpoints
3 Objectives and endpoints
The exploratory endpoint related to 
ITP bleeding score has been 
changed to “ITP BAT bleeding 
events and severity by visit”.
Updated to specify the bleeding 
assessment tool to be used and 
clarification of the timepoint.
1.1 Synopsis, Objectives 
and endpoints
3 Objectives and endpoints
The exploratory endpoints related 
to the effect of rozanolixizumab on 
health-related quality of life 
(HRQoL) have been modified.
Updated to provide clarity and to 
include missing details from 
previous version of the protocol.
1.1 Synopsis, Objectives 
and endpoints
3 Objectives and endpoints
The exploratory endpoints related 
to the effect of rozanolixizumab on 
patient reported outcomes (PROs) 
have been modified.
Updated to provide clarity and to 
include missing details from 
previous version of the protocol.
1.1 Synopsis, Objectives 
and endpoints
3 Objectives and endpoints
The exploratory objective has been 
amended from “To assess the 
plasma concentrations of 
rozanolixizumab” to “To assess the 
pharmacokinetics of 
rozanolixizumab”.
Updated to correct an error.
1.1 Synopsis, Objectives 
and endpoints
3 Objectives and endpoints
Pharmacodynamic (PD) endpoints 
were updated to include “total 
serum IgG” and “serum IgG”.
To include missing details from 
previous version of the protocol.
1.1 Synopsis, Objectives 
and endpoints
3 Objectives and endpoints
1.3 Schedule of Activities, 
Table 1-4
The “Physical Fatigue Instrument” 
has been changed to the 
“FATIGUE-PRO Physical Fatigue 
scale”.
Updated to indicate the correct 
name of the PRO.
1.1 Synopsis, Overall 
design
“Visit 1” has been added to clarify 
when Screening occurs. 
Updated to provide clarity.
1.1 Synopsis, Overall 
design
Details have been added to explain 
that a 
 total dose 
corresponds to an average 
 
dose in a participant weighing 
70kg.
Updated to provide clarity.
1.1 Synopsis, Overall 
design
1.1 Synopsis, Treatment 
groups and duration, 
Table 1-2, footer
Additional wording has been 
provided for clarification on the 
action taken for study participants 
on the lowest dose level with a 
platelet count between >200×109/L 
and <400×109/L.
This update has been included to 
consider that no dose reduction to 
less than 
(fixed dose) is 
set.e
1.1 Synopsis, Treatment 
groups and duration
Additional wording has been 
provided to explain that placebo 
Updated to provide clarity.
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th
an
n
app
psis, Over
app
psis, Over
p


UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 196 of 220
Section # and Name
Description of Change
Brief Rationale
will be administered at volumes 
matching the rozanolixizumab arm.
1.1 Synopsis, Overall 
design
4.1 Overall design
The study hold criteria was 
amended to remove the following 
wording: “as soon as” and add 
“clearly”.
Updated to provide clarity for the 
stopping rule.
1.1 Synopsis, Overall 
design
4.1 Overall design
For US and Canada only: The 
stopping rule was updated from 
when 3 study participants 
experience SAEs of the same type 
within the first 15 participants who 
have received 3 doses of IMP 
across TP0003 and TP0006 to 
when 3 study participants 
experience any SAE within the 
first 15 study participants who 
have received at least one dose of 
IMP across TP0003 and TP0006. 
Clarification that the stopping rule 
is applicable unless the SAE is 
clearly unrelated to study drug.
Inclusion of the local US/CAN
protocol amendment. Updated text 
per FDA request to change the 
study stopping rule.
1.1 Synopsis, Number of 
Participants
The number of additional 
participants that may be recruited 
into the study was changed from 75 
to 60. In addition, the maximum 
total sample size has been changed 
from 105 to 90.
Number of study participants had 
been changed based on revised 
sample size calculation method and 
assumptions.
1.3 Schedule of Activities, 
Table 1-3
For participants in Japan only: 
Footnotes c and d were amended to 
include “if applicable as per local 
guidance in Japan”
Updated to provide further clarity.a
1.3 Schedule of Activities, 
Table 1-3
Assessment of 12-lead ECG: 
Footnote i has been added to Visit 
6 and EOS Visit.
Updated to correct an error.
1.3 Schedule of Activities, 
Table 1-4
Assessment of PGI-C has been 
removed from Visit 2 (Baseline).
Entered in error as “change” cannot 
be assessed at baseline.
1.3 Schedule of Activities, 
Table 1-4
For participants in Japan only: 
Chest X-ray assessment added to 
EW visit and EOS visit.
To confirm safety at study 
termination.a
1.3 Schedule of Activities, 
Table 1-4
Blood sampling for plasma 
concentration of rozanolixizumab 
has been removed from the EOS 
visit. 
Expected to be below the limit of 
quantification.
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dule of A
pp


UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 197 of 220
Section # and Name
Description of Change
Brief Rationale
1.3 Schedule of Activities, 
Table 1-4
Footnote g was added to clarify 
that the platelet count assessed by 
the local laboratory can be done -1 
day for the Baseline (Visit 2) and 
for Week 3 (Visit 6). For 
subsequent dosing visits, the last 
two available platelet counts can be 
considered. Subsequent footnotes 
were reordered.
Updated to clarify the platelet 
count assessment.b
1.3 Schedule of Activities, 
Table 1-4
For participants in Japan only: 
Footnote m: Wording pertaining to 
T-SPOT.TB test may be performed 
as an alternative. 
To add the T-SPOT test as a 
recommended IGRA test in 
addition to the QuantiFERON test.a
1.3 Schedule of Activities, 
Table 1-4
For participants in Japan only: 
Footnote n: Wording pertaining to 
chest X-ray be performed only at 
sites in countries at high risk for 
TB has been removed. New 
wording underlining “Chest x-ray 
to be performed also EW and 
EOS” has been added. 
To confirm safety at study 
termination. a
1.3 Schedule of Activities, 
Table 1-4
For participants in Japan only: 
Footnote o: New footnote 
underlining that a chest X-ray is to 
be performed only in the event of 
an EW and EOS Visit, has been 
added.
To confirm safety at study 
termination. a
1.3 Schedule of Activities, 
Table 1-4
Footnote p has been updated to 
include EOS Visit.
Updated to correct an error.
1.3 Schedule of Activities, 
Table 1-4
Footnote z (previously footnote y): 
Footnote changed from “prior to 
the first dose” to “prior to dosing”.
Updated to provide further clarity.
2.2 Background
“Ongoing” has been removed from 
Study UP0060.
Clinically complete with study 
reporting ongoing
4.1 Overall Design
The following sentence 
“Previously, in TP0001, a 15mg/kg 
dose was evaluated. In TP0003, a 
single fixed-unit dose equivalent to 
 will be administered at 
the Baseline Visit. Following the 
initial dose, study participants will 
then receive a fixed-unit dose of 
equivalent to 
 
rozanolixizumab or placebo, every 
To avoid repetition.
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Design
plic
Design
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 198 of 220
Section # and Name
Description of Change
Brief Rationale
two weeks until Week 23.” has 
been deleted
4.1 Overall Design
A new sentence has been added to 
explain that contingency measures 
during a pandemic and other 
exceptional circumstances have 
been included.
Contingency measures have been 
implemented to ensure study 
participant safety in response to the 
COVID-19 pandemic causing the 
inability for sites to adhere to 
protocol visits and assessments.
4.1 Overall Design
The number of sites has been 
changed from 50 to 70. In addition, 
the maximum number of evaluable 
study participants has been 
changed from 105 to 90.
Increased to reflect the number of 
potential sites.
Number of study participants had 
been changed based on revised 
sample size calculation method and 
assumptions.
4.4 End of study definition
Clarified that only study 
participants not rolling over into 
TP0004 will have an EOS Visit 
performed 8 weeks after the final 
dose of IMP, or upon 
discontinuation of the study.
Updated for consistency within the 
protocol.
5.1 Inclusion Criteria
For participants in Japan only: 
Criterion #1, now 1a: New wording 
has been included to provide 
details on the consent requirements 
for participants aged <20 years of 
age. 
In accordance with local 
regulations in Japan. a
5.1 Inclusion criteria
Criterion #4 now 4a, has been 
amended to include documented 
intolerance or insufficient response 
to a minimum of two standard of 
care ITP medications.
Global implementation of an 
ANSM request and implement 
feedback received from the FDA.
5.1 Inclusion criteria
Criterion #6 now 6a, has been 
amended to remove 
“immunosuppressive”.
Updated to be consistent with 
Table 6-2.
5.2 Exclusion criteria
Criterion #5 now 5a, has been 
updated to remove reference to 
IMP or comparative drugs (and/or 
an investigational device).
Updated to be consistent across the 
Phase 3 rozanolixizumab clinical 
program.
5.2 Exclusion criteria
Criterion #7 now 7a, has been 
amended to remove “bacterial or 
viral infection” and “untreated
H. pylori infection” has been 
added.
Updated for exclusion criteria 
clarification. a
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plic
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ic


UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 199 of 220
Section # and Name
Description of Change
Brief Rationale
5.2 Exclusion criteria
Criterion #8 now 8a, was updated 
to ensure the criterion was 
applicable to prior to the “first” 
dose.
Updated for exclusion criteria 
clarification.
5.2 Exclusion criteria
Criterion #11 now 11a, was 
amended to “Study participant has 
any of the following active GI 
disorders: inflammatory bowel 
disease, GI ulceration or 
diverticulitis.”
No scientific reason to exclude 
patients with history of said 
disorders.
5.2 Exclusion criteria
For participants in Japan only: 
Criterion #20a has been amended 
to include “if applicable as per 
local guidance” and remove “per 
local guidance” for a lack of 
documented vaccination records.
Updated for exclusion criteria 
clarification.a
5.2 Exclusion criteria
Criterion #21 now 21a, was 
updated to ensure the criterion was 
applicable to the “final” dose.
Updated for exclusion criteria 
clarification.
5.2 Exclusion criteria
Criterion #23 now 23a, has been 
updated to clarify that study 
participants with treatment with 
rituximab more than 6 months 
prior to Visit 2 (Baseline Visit) are 
excluded if B cells have not 
returned to normal, irrespective of 
time.
Allowing recovery of B cell 
function is preferable regardless of 
the lapsed time. e
5.2 Exclusion criteria
Criterion #24 now 24a, has been 
amended to include a 
cross-reference to rescue therapy
Updated for exclusion criteria 
clarification.
5.2 Exclusion criteria
Criterion #28 now 28a, has been 
amended to include “at the 
Screening Visit”.
Updated for exclusion criteria 
clarification. e
5.2 Exclusion criteria
Criterion #31 now 31a, has been 
amended to include a specific 
timepoint, ie, Baseline.
Updated for exclusion criteria 
clarification.
5.2 Exclusion criteria
Criterion #33 now 33a, has been 
amended to include a specific 
timepoint, ie, Screening and the 
order of text has been reordered. In 
addition, “understood and” has 
been deleted.
Updated for exclusion criteria 
clarification.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 200 of 220
Section # and Name
Description of Change
Brief Rationale
5.2 Exclusion criteria
Criterion #34 now 34a, has been 
amended to include "at the 
Screening Visit."
Updated for exclusion criteria 
clarification.
5.2 Exclusion criteria
Criteria #39 now 39a, was updated 
to replace family history with 
“current or medical history”.
Updated for exclusion criteria 
clarification.
5.2 Exclusion criteria
Criteria #41 now 41a, was updated 
to specify heart rate using 
Fridericia’s formula (QTcF), and to 
correct the visit to “Baseline Visit”.
QTc was not specific enough.
5.2 Exclusion criteria
Criteria #43 now 43a, has been 
updated to only exclude major 
surgeries, and only whilst 
participants are in the study.
Updated to be consistent across the 
Phase 3 rozanolixizumab clinical 
program.
5.2 Exclusion criteria
For participants in Japan only: 
A new criterion, #44, has been 
added: Study participant has 
undergone a partial splenic artery 
embolization in the 6 months prior 
to Baseline Visit. Study 
participants with evidence of 
functional asplenia should be 
managed clinically as a 
splenectomized participant 
(eg, vaccination, antibiotics 
prophylaxis) as per local guidance.
Added as this procedure might be 
used for treatment of ITP in Japan 
and certain exclusions need to be 
applied. a
5.2 Exclusion criteria, 
Table 5-1
The period relative to the Baseline 
Visit has been updated for 
rituximab in line with Exclusion 
Criterion 23a.
Updated for required treatment-free 
periods. e|
5.2 Exclusion criteria, 
Table 5-1
Inebulizumab was added to the 
table requiring a 6-month 
treatment-free period prior to 
Baseline, and B-cell counts within 
the normal range.
Updated for clarification of 
prohibited medications and 
required treatment-free periods.
5.2 Exclusion criteria, 
Table 5-1
TPO-RAs examples of 
Eltrombopag and Avatrombopag 
were removed. 
Updated for clarification of 
prohibited medications and 
required treatment-free periods. d
5.4 Screen failures
New wording has been included 
pertaining to additional 
rescreening.
Updated to provide clarity and be 
consistent with study design and 
remainder of protocol.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 201 of 220
Section # and Name
Description of Change
Brief Rationale
6 Study Treatments, 
Table 6-1
Canada has been added to 
Packaging and label specification. 
Updated to remain consistent 
across the ITP Phase 3 clinical 
program.
6.2 Measures to minimize 
bias: randomization and 
blinding
The following text has been added 
to: The randomization number will 
be incorporated from the IRT into 
the eCRF by automatic data 
transfer.
Updated to provide further clarity.
6.2.1.1: Maintenance of 
study treatment blind
Amended to allow disclosure of 
platelet count results to study 
participants.
It is deemed necessary information 
for participants when engaging in 
activities of daily living.
6.2.1.1: Maintenance of 
study treatment blind
The following sentence was added 
“An independent Quantitative 
Clinical Pharmacologist/Modeling 
and Simulation Scientist may have 
access to the randomization code to 
review unblinded PK, platelet and 
serum IgG data.” 
Added to allow modelling 
activities regarding potential 
pharmacokinetic/pharmacodynamic 
analysis as specified in the 
statistical section to be started by 
and independent scientist.
6.2.1.1: Maintenance of 
study treatment blind
7.1.4: Temporary IMP 
discontinuation
Clarification that treatment will be 
temporarily discontinued for any 
participant with IgG levels below 
1g/L on any occasion.
Clarification of formal and 
informal unblinding and the role of 
the unblinded Medical Monitor.
Updated to clarify when treatment 
discontinuation is required, 
unblinding, and the role of the 
unblinded Medical Monitor.b
6.4.1 Permitted 
concomitant treatments 
(medications and 
therapies), Table 6-2
Clarification of oral corticosteroid 
dose. 
Updated to clarify permitted 
concomitant medications. b
6.4.1 Permitted 
concomitant treatments 
(medications and 
therapies), Table 6-2
Addition of Eltrombopag, 
Avatrombopag and Fostamatinib at 
any dose as permitted concomitant 
treatments. 
Updated to clarify permitted 
concomitant medications.d
6.4.1 Permitted 
concomitant treatments 
(medications and 
therapies), Table 6-2
The following footnote was added 
“a Stable dose is defined as either 
the same dose and frequency of the 
respective medication taken for the 
period of time defined in 
Table 6-2, or no dose of the 
respective medication taken for the 
period of time as defined in 
Table 6-2.”
Added to provide additional clarity 
on the protocol requirements 
related to the stable dose of the 
allowed concomitant treatments.
PUBLIC COPY 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 202 of 220
Section # and Name
Description of Change
Brief Rationale
6.4.1 Permitted 
concomitant treatments 
(medications and 
therapies)
Applicable to Japan only: The 
following wording has been 
removed: “The use of medicinal 
cannabidiols and medicinal 
marijuana (prescribed by a 
physician) is also permitted. When 
applicable, the study participant 
must be on a stable dose of 
cannabidiols and/or medicinal 
marijuana for 
 prior to 
Screening and remain stable for the 
duration of the study.”
These drugs are prohibited by law 
in Japan. a
6.4.2 Prohibited 
concomitant treatments 
(medications and 
therapies)
Clarification of corticosteroids.
Updated to clarify prohibited 
concomitant medications. b
6.4.2 Prohibited 
concomitant treatments 
(medications and 
therapies)
Addition of Romiplostim as 
prohibited treatment.
Updated to clarify prohibited 
concomitant medications. a
6.4.2 Prohibited 
concomitant treatments 
(medications and 
therapies)
Removal of TPO-RA as prohibited 
treatment.
Updated to clarify prohibited 
concomitant medications. a
6.4.2 Prohibited 
concomitant treatments 
(medications and 
therapies)
New wording has been included 
explaining the use of prohibited 
concomitant treatment will lead to 
permanent discontinuation from 
IMP. Subsequently, participants 
should complete the assessments 
outlined for the EW Visit and enter 
the SFU Period.
Updated for clarification of 
prohibited medications.
6.4.3 Rescue Therapy
Additional details related to 
platelet transfusion, systemically 
administered corticosteroids, and a 
definition of a high dose of 
corticosteroids have been included.
Updated to clarify rescue therapy.c
7.1.3 Discontinuation of 
IMP due to other adverse 
events or medical 
condition
New wording has been included on 
the withdrawal of study participant 
during the treatment period and the 
requirement to complete 
assessments outlined in the Early 
Withdrawal Visit. 
Updated to provide further clarity 
on study visits following 
withdrawal.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 203 of 220
Section # and Name
Description of Change
Brief Rationale
7.1.4 Temporary IMP 
discontinuation
Criterion #2, #3, #4, and #5 were 
amended.
In addition, details have been 
added for participants that have 
suspected or confirmed COVID-
19.
Updated to provide clarity and 
remain consistent.
7.2 Participant 
discontinuation/withdrawal 
from the study
This section was updated to reorder 
withdrawal criteria and remove 
repetitive information.
Updated to provide clarity and be 
consistent with study design and 
remainder of protocol.
7.3 Lost to follow up
This section was updated to 
remove repetitive information.
To avoid repetition.
8 Study Assessments and 
Procedures
A new paragraph describing 
contingency measures during a 
pandemic and other exceptional 
circumstances has been included.
Contingency measures have been 
implemented to ensure study 
participant safety in response to the 
COVID-19 pandemic causing the 
inability for sites to adhere to 
protocol visits and assessments.
8.1.1 Platelet counts
Study endpoints related to platelet 
counts were updated to match the 
updates made in Sections 1.1 and 
3.
To be consistent with the rest of the 
protocol.
8.1.1 Platelet counts
The following sentence was 
modified to clarify that the analysis 
was not for all clinical response 
variables: “The Response and 
Complete Response variables will 
be assessed only for visits for 
which both platelet counts and the 
ITP bleeding score are assessed 
(with the exception of the 
confirmatory platelet assessments 
which may be obtained at any visit 
(scheduled or unscheduled) 
provided that they meet the criteria 
below).”
Updated to provide clarity.
8.1.2 ITP bleeding score
The following was added ‘with 
grading of severity’ to clarify the 
definition SMOG.
Updated to include missing 
information.
8.1.3 Patient Reported 
Outcomes
The list of PROs has been updated 
to replace the “Physical Fatigue 
Instrument” by the “FATIGUE-
PRO Physical Fatigue scale”.
To indicate the correct name of the 
PRO.
8.1.3.1 ITP-PAQ
Details have been added to explain 
the addition of the ITP-PAQ 
Corrected to clarify the variable.
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bleeding 
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bleeding 
pl


UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 204 of 220
Section # and Name
Description of Change
Brief Rationale
Symptoms score as a secondary 
efficacy endpoint.
8.1.3.3 FATIGUE-PRO 
Physical Fatigue Scale
The “Physical Fatigue Instrument” 
has been replaced by the 
“FATIGUE-PRO Physical Fatigue 
scale”.
To indicate the correct name of the 
PRO.
8.2.5 Assessment and 
management of TB and TB 
risk factors
A cross reference to the exclusion 
criteria was corrected: Exclusion 
Criterion 0 was updated to 
exclusion criterion 9.
Updated to correct an error.e
8.2.5.1 Tuberculosis 
assessment
Wording for Monitoring for TB 
during the study has been updated 
to clarify that study participants 
who have withdrawn from the 
study return for the EW visit and 
complete all EOS assessments.
Updated to correct an error.
8.2.5.1 Tuberculosis 
assessment
TB signs and symptoms 
questionnaire: “and must receive 
prophylactic LTB infection 
therapy” has been deleted.
To provide further clarity.
8.2.5.1 Tuberculosis 
assessment
Applicable to Japan only: New 
wording for TB assessment by 
IGRA has been added: the 
preferred screening test is IGRA 
performed at a Central Laboratory 
by QuantiFERON tube test, “or 
using a T-SPOT.TB test at each 
site”
To add the T-SPOT test as a 
recommended IGRA test in 
addition to QuantiFERON test.a
8.2.5.1 Tuberculosis 
assessment
Applicable to Japan only: New 
wording for TB assessment by 
chest x-ray has been included: 
“Although the incidence of TB is 
low in Japan, chest X-rays should 
be performed for all study 
participants.”
The following text has been 
amended: “A chest X-ray or other 
imaging test at unscheduled 
timepoints (see Section 1.3) should 
be performed only if indicated (eg, 
presence of signs and symptoms 
suggestive of TB, close exposure to 
persons with TB), and interpreted 
by a qualified specialist (ie, 
radiologist or pulmonologist)”
To confirm safety regarding 
various chest diseases. a
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application


UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 205 of 220
Section # and Name
Description of Change
Brief Rationale
8.2.5.2 Tuberculosis 
management
Active TB or nontuberculous 
mycobacterium infection:
New wording has been included 
stating study participants should be 
encouraged to “enter the SFU 
period” and “attend Visit 29”.
Updated to clarify procedures on 
active TB or nontuberculous 
mycobacterium infection.
8.2.6 Splenectomized 
study participants 
Applicable to Japan only: 
Additional wording has been 
included: “if applicable” and “as 
per local requirements”
Updated to provide further clarity.a
8.2.6 Splenectomized 
study participants
Wording specific to 
splenectomized participants 
receiving adequate vaccination 
within 4 years of enrollment or 
prior to enrollment to avoid the 
treatment interruption has been 
included.
Updated to provide further clarity.
8.3.8 Adverse events of 
special monitoring
A sentence has been added to 
clarify that an AESM is not 
necessarily a serious adverse event 
unless one of the seriousness 
criteria defined in the Appendix 3.
Updated to provide further clarity.
8.8.2 Immunology
Text updated to specify that serum 
complements (C3, C4), plasma 
complements (C3a, C5a), and 
serum cytokines are collected 
4 hours postdose at Baseline and at 
Week 23.
Updated to provide further clarity 
and be consistent with the rest of 
the protocol.
8.9 Exploratory 
biomarkers
Duplicate details pertaining to 
sample collection, processing, 
storage, labeling, and shipping 
have been deleted.
To remove repetition.
9.1 Definition of analysis 
sets
Text around the analysis of the PD, 
efficacy and immunologic 
variables has been updated and 
moved to be under the definition of 
the Safety Set (SS).
To clarify that all efficacy will be 
analyzed on the Randomized 
Set (RS) and the PD and 
immunology will be analyzed on 
the SS analysis set, unless 
otherwise specified.
9.1 Definition of analysis 
sets
The definition of the Full Analysis 
Set (FAS) has been updated.
Updated to be consistent with the 
SAP.
9.1 Definition of analysis 
sets
Updated the analysis set for the 
“Pharmacodynamic data” and the 
“Pharmacodynamic Per Protocol 
Set” analysis to the SS.
Updated to clarify that the 
pharmacodynamics will be 
analyzed in the safety set (all 
randomized study participants who 
received at least one dose of IMP).
UBLIC COPY 
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ion


UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 206 of 220
Section # and Name
Description of Change
Brief Rationale
9.2 General statistical 
considerations
A sentence was added to explain 
that data handling conventions for 
data affected by COVID-19 will be 
detailed fully in the SAP.
Added to confirm that the potential 
effects of COVID-19 on the data 
analysis will be addressed.
9.3.1 Analysis of the 
primary efficacy/primary 
endpoint
The primary efficacy endpoint was 
updated to match the updates made 
in Sections 1.1 and 3.
To be consistent with the rest of the 
protocol.
9.3.1 Analysis of the 
primary efficacy/primary 
endpoint
The description of the primary 
analysis was updated. In addition, 
the test statistic for the 
combination test(s) was updated 
from t-test to Cochran-Mantel-
Haenszel chi-square. 
Updated to correct an error in the 
previous version.b
9.3.1 Analysis of the 
primary efficacy/primary 
endpoint
Table 9-1: The primary efficacy 
endpoint was updated to match the 
updates made in Sections 1.1 and 
3. In addition, the intercurrent 
event strategy for the sensitivity 
analysis was amended.
To be consistent with the rest of the 
protocol.
9.3.1 Analysis of the 
primary efficacy/primary 
endpoint
Table 9-1: Updated the analysis of 
the primary endpoint.
To provide further clarity.
9.3.1 Analysis of the 
primary efficacy/primary 
endpoint
Table 9-1: Added a sensitivity 
analysis for the same endpoint, 
using the same analysis set (RS), 
but different methods for imputing 
missing values.
To confirm the robustness of the 
primary result.
9.3.1 Analysis of the 
primary efficacy/primary 
endpoint
Table 9-1: Included a 
‘supplemental analysis’ for the 
difference in the proportion of 
responders using Fisher’s Exact 
test.
To confirm the result should the 
placebo rate be low.
9.3.2 Analysis of the 
secondary efficacy 
endpoints
The secondary efficacy endpoints 
were updated to match the updates 
made in Sections 1.1 and 3.
To be consistent with the rest of the 
protocol.
9.3.2 Analysis of the 
secondary efficacy 
endpoints
Table 9-2: Estimands for secondary 
endpoints: Details for the “patient 
reported outcomes” have been 
updated.
To provide further clarity.
9.3.2 Analysis of the 
secondary efficacy 
endpoints
Table 9-2: Updated the analysis of 
the secondary endpoint 
“Cumulative number of weeks with 
Clinically Meaningful Platelet 
Response of ≥50x109/L over the 
To provide further clarity.
UBLIC COPY 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 207 of 220
Section # and Name
Description of Change
Brief Rationale
24-week treatment period” to 
include the geographical region.
9.3.2 Analysis of the 
secondary efficacy 
endpoints
Table 9-2: Updated the analysis of 
the secondary endpoint “Time to 
first Clinically Meaningful Platelet 
Response of ≥50x109/L: time from 
starting treatment to achievement 
of first response of ≥50x109/L” to 
include the geographical region.
To provide further clarity.
9.3.2 Analysis of the 
secondary efficacy 
endpoints
Table 9-2: Updated the analysis of 
the secondary endpoint “Clinically 
Meaningful Platelet Response of 
≥50x109/L by Day 8”
To provide further clarity.
9.3.2 Analysis of the 
secondary efficacy 
endpoints
Table 9-2: Updated the analysis of 
the secondary endpoint “Response 
defined as platelet count ≥30x109/L
and at least a 2 fold increase of the 
Baseline count confirmed on at 
least 2 separate occasions at two 
adjacent nominal visits at least 7 
days apart, and absence of 
bleeding”
To provide further clarity.
9.3.2 Analysis of the 
secondary efficacy 
endpoints
Table 9-2: Updated the sensitivity 
analysis of the secondary endpoint 
“Response defined as platelet count 
≥30x109/L and at least a 2 fold 
increase of the Baseline count 
confirmed on at least 2 separate 
occasions at two adjacent nominal 
visits at least 7 days apart, and 
absence of bleeding” to include the 
geographical region.
To provide further clarity.
9.3.2 Analysis of the 
secondary efficacy 
endpoints
Table 9-2: The following 
secondary endpoints were deleted: 
“Complete Response defined as: 
platelet count ≥100x109/L 
confirmed at two adjacent nominal 
visits at least 7 days apart, and 
absence of bleeding.”, “Clinically 
meaningful Response defined as: 
platelet count ≥50x109/L.” and 
“Duration of Clinically Meaningful 
Response: measured from 
achievement of first Response to 
loss of Response (loss of Response 
To be consistent with the rest of the 
protocol as these are no longer 
secondary endpoints.
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03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 208 of 220
Section # and Name
Description of Change
Brief Rationale
defined as platelet count 
<50x109/L).”
9.3.2 Analysis of the 
secondary efficacy 
endpoints
The study endpoint related to 
ITP-PAQ Symptoms Score has 
been updated.
To provide further clarity.
9.3.2 Analysis of the 
secondary efficacy 
endpoints
Updated the analysis of the 
secondary endpoint “Change from 
Baseline to Week 25, including all 
intermediate timepoints, in ITP 
PAQ Symptom score” to include 
the geographical region.
To provide further clarity.
9.3.3.1 Analysis of 
pharmacokinetic endpoint
Language was updated to be in 
agreement with the SAP, and state 
that individual plasma 
concentration data will be 
summarized up to Week 4 where 
most participants will have not 
followed down titration yet, if any.
Updated for clarification. Further 
details will be described in the 
SAP.
9.3.3.1 Analysis of 
pharmacokinetic endpoint
The following sentence was added. 
“Summaries by geographical 
region may be performed.”
To provide further clarity.
9.7 Planned interim 
analysis and data 
monitoring
Details were added to explain that 
the interim analysis will be 
conducted on combined data from 
TP0003 and TP0006. The text for 
the sample size re-estimation 
procedure was modified to allow 
for the option of maintaining the 
minimum sample size or increasing 
it. An additional sentence was 
added to state that no decrease in 
sample size will be permitted.
The futility stopping rule was 
amended to “The study may stop 
for futility if the difference in 
response rates of the combined 
data from TP0003 and TP0006 is 
<5%, ie, the rate in the 
experimental arm is no less than 
5% greater than the placebo arm.”
To provide information for the 
proposal to potentially combine 
information from TP0003 and 
TP0006 for the estimand of the 
observed treatment effect in the 
assessment of futility and sample 
size re-estimation for Stage 2. 
Also, to update the decision criteria 
for futility to the stricter 5% level.
9.7.2 Early stopping for 
futility
The futility stopping rule was 
amended to “The futility stopping 
rule (non-binding) utilized for the 
study requires that at stage 1 the 
response in the rozanolixizumab 
Updated due to an amendment to 
the futility decision rule.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 209 of 220
Section # and Name
Description of Change
Brief Rationale
arm is less than 5% greater than the 
placebo arm.”
9.8 Determination of 
sample size
Response rates were added from a 
publication (Kuter et al, 2008)
To provide further clarity.
9.8 Determination of 
sample size
The alpha level has been changed 
from 0.05 (2-sided) to 0.025 
(1-sided).
The 1-sided test is more correct 
owing to the nature of the adaptive 
design.
9.8 Determination of 
sample size
Details about the interim analysis 
were modified to describe the 
combination of studies TP0003 and 
TP0006. In addition, it was 
clarified that the Stage 1 and Stage 
2 p-values for the combination test 
will be obtained solely on an 
analysis of the primary endpoint 
for TP0003.
To increase the precision of the 
estimate of the observed treatment 
effect for assessment of futility and 
sizing of Stage 2, data from 
TP0003 and TP0006 will be 
combined at the interim analysis 
provided the studies recruit to a 
similar timeline.
9.8 Determination of 
sample size
Table 9-3: The expected sample 
size for TP0003 has been updated.
Number of study participants had 
been changed based on revised 
sample size calculation method and 
assumptions.
9.8 Determination of 
sample size
Details of the simulation results 
were updated.
Updated following the reduction in 
the sample size cap of 
90 participants and the change in 
the futility stopping rule of more 
than 5% better than placebo.
10.1.3 Informed consent 
process
For participants in Japan only: 
New wording has been included to 
provide details on the consent 
requirements for participants aged 
<20 years of age.
In accordance with local 
regulations in Japan. a
10.2, Appendix 2: Clinical 
laboratory tests
Table 10-1: Footnotes b, c, d, e, 
and g added to clarify collection 
timepoints and requirements for 
protocol-required safety laboratory 
assessments.
Updated for clarification.b
10.2, Appendix 2: Clinical 
laboratory tests
Table 10-1: Footnote h updated to 
include post baseline results for 
vaccination specific titers
To ensure blinding is consistent 
throughout all studies in the 
rozanolixizumab clinical program.
10.6 Appendix 6: Liver 
safety – suggested actions 
and follow-up assessments
Table 10-3: The following wording 
has been removed: These criteria 
are not directly applicable to 
TP0003 because it is a single dose 
study; however, these criteria are 
indirectly applicable because upon 
completion of study TP0003, the 
To remove wording that was left 
from a previous version and to 
clarify the language for suggested 
actions.b
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 210 of 220
Section # and Name
Description of Change
Brief Rationale
study participants are to be 
provided a chance to enroll in the 
OLE study TP0004.
Clarification of language related to 
acetaminophen contribution to 
liver injury and removal of 
wording pertaining to requirements 
in China. 
10.6 Appendix 6: Liver 
safety – suggested actions 
and follow-up 
assessments, References
The following reference was 
removed:
James LP, Letzig L, Simpson PM, 
Capparelli E, Roberts DW, Hinson 
JA, et al. Pharmacokinetics of 
acetaminophen-protein adducts in 
adults with acetaminophen 
overdose and acute liver failure. 
Drug Metab Dispos. 2009; 
37:1779-84
Updated to maintain consistency 
within the protocol. a
10.8, Appendix 8: 
Country-specific 
requirements
New wording on specific 
requirements for Japan have been 
added.
In accordance with local 
regulations and actual condition of 
medical care. a
10.9 Appendix 9: 
Abbreviations and 
trademarks
Additional abbreviations and 
definitions were added: ADE, DD, 
and SADE.
Updated to reflect the parameters 
measured in the study.
10.13, Appendix 13: 
ITP-PAQ
Removed an additional version of 
the ITP-PAQ questionnaire.
Updated to remove an additional 
version of the questionnaire that 
was accidentally included.b
10.15, Appendix 15: 
FATIGUE-PRO Physical 
Fatigue scale
The “Physical Fatigue Instrument” 
has been replaced by the 
“FATIGUE-PRO Physical Fatigue 
scale”.
Updated questionnaire.
10.15, Appendix 15: 
Physical Fatigue 
Instrument
The Physical Fatigue PRO was 
updated to a new version.
Updated questionnaire.b
10.15, Appendix 15: 
Physical Fatigue 
Instrument
Mental fatigue and fatigability 
were removed.
Updated questionnaire.e
10.22, Appendix 22: 
Management of headaches
Text added to clarify that treatment 
may be temporarily put on hold if a 
study participant experiences an 
AE of a severe headache that is 
considered related to the IMP in 
the opinion of the investigator, and 
To add clarity.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 211 of 220
Section # and Name
Description of Change
Brief Rationale
is not resolved prior to the next 
scheduled IMP.
10.23, Appendix 23: 
Management of diarrhea
Definition of severe (grade 3) 
diarrhea has been updated.
To add clarity. 
10.23, Appendix 23: 
Management of diarrhea
Modification of language regarding 
stool sample collection for 
participants reporting severe 
diarrhea.
To clarify when stool samples may 
be collected. b
10.24 Appendix 24: 
Management of infusion 
reactions or 
hypersensitivity reactions
Modification of language regarding 
potential infusion related reactions.
Updated to provide further clarity.
10.25 Appendix 25: 
Management of Infections 
and 
Hypogammaglobulinemia
The following sentence was 
modified to state that study 
participants who discontinue must 
perform the EW Visit, enter the 
SFU Period and complete the EOS 
Visit. Study participants MUST 
discontinue IMP, perform the EW 
Visit, enter the SFU Period and 
complete the EOS Visit if any of 
the following events occur:
To add clarity.
10.25 Appendix 25: 
Management of Infections 
and 
Hypogammaglobulinemia
Modification of language regarding 
the Medical Monitor to clarify they 
are unblinded.
The following sentence was 
modified to include “must”: 
Treatment must be temporarily 
discontinued for a study participant 
who develops an event of 
hypogammaglobulinemia with a 
serum total IgG of <1g/L 
irrespective of infection.
The following sentence was added 
“Mock infusions will be 
administered to maintain the blind
in case of low IgG levels (see 
Section 7.1.4).”
Updated to be consistent across the 
Phase 3 rozanolixizumab clinical 
program.
10.26 Appendix 26 
Protocol Amendment 
History 
Protocol amendment 1 (global 
amendment) has been added. 
General update.
11 References
An additional reference has been 
added, as cited in Section 9.8.
General update.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 212 of 220
Section # and Name
Description of Change
Brief Rationale
11 References 
An additional reference has been 
added, as cited in Section 10.8. 
General update.a
a This update was previously incorporated to local protocol amendment 1.2.
b This update was previously incorporated to local protocol amendments 1.1, 1.2 and 1.3.
c This update was previously incorporated to local protocol amendment 1.3.
d This update was previously incorporated to local protocol amendments 1.1. and 1.2.
e This update was previously incorporated to local protocol amendments 1.2. and 1.3.
Amendment 1 (21 Nov 2019)
Overall Rationale for the Amendment
The primary reason for this protocol amendment is to incorporate the feedback from the 
 
. 
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union.
Section # and Name
Description of Change
Brief Rationale
Global
Minor administrative, formatting 
and typographical changes have 
been made.
Updated to provide clarity 
and be consistent with 
remainder of protocol.
Global
The term “Observation Period” has 
been removed or replaced by 
“Treatment Period” where 
applicable. 
Updated to provide clarity 
and be consistent with 
remainder of protocol.
Title page
The Sponsor address was changed 
from UCB Biopharma SPRL to 
UCB Biopharma “SRL”
Administrative update.
1.1 Synopsis
3 Objectives and 
Endpoints
4.1 Overall Design
8.1.1 Platelet counts
9.3.1 Analysis of the 
primary efficacy/primary 
endpoint
The wording for primary endpoint 
has been amended: the word “from” 
was replaced with “for”. 
Updated to provide 
clarity. 
1.1 Synopsis
The following wording in reference 
to 8 out of 12 weeks has been 
amended to replace “in” with “for 
at”: Clinically Meaningful Platelet 
Count of ≥50x109/L for at least 8 
out of 12 weeks during the last 12 
Updated to provide 
clarity.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 213 of 220
Section # and Name
Description of Change
Brief Rationale
weeks of the Treatment Period 
(Weeks 13 to 25).
1.1 Synopsis
4.1 Overall Design
Additional wording for study 
stopping rules have been included. 
Per FDA request to 
include details on study 
stopping rules. 
1.1 Synopsis
Under the subsection, Number of 
participants, the following text, 
“after stage 1” has been replaced by 
“at this stage”. In addition, new 
wording “during the interim 
analysis, recruitment will be 
ongoing” has been included.
Updated to provide 
clarity.
1.1 Synopsis
Under the subsection, Total groups 
and duration, the description of a 
prescreening period has been 
changed to Prolonged Screening 
Period. 
Updated to provide clarity 
and consistency. 
1.3 Schedule of Activities
Table 1-3: Table title, the schedule 
and corresponding footnotes have 
been updated.
Updated to provide clarity 
and be consistent with 
study design.
1.3 Schedule of Activities
Table 1-4: Table heading has been 
amended to replace Observation 
Period with “Treatment Period” 
and include the Safety Follow-Up 
Period.
Updated to provide clarity 
and be consistent with 
remainder of protocol.
1.3 Schedule of Activities
Table 1-4: Urine pregnancy test 
was added to Week 25 (Visit 28) 
was added and footnote f was 
applied to this visit and removed 
from EOS visit. 
As per study design, 
enrollment into the OLE 
study, TP0004, should be 
conducted on the same 
day as Visit 28 (Week 
25), and urine pregnancy 
test will be used to check 
participant’s eligibility. 
1.3 Schedule of Activities
Table 1-4: Vital signs will be 
measured and collected at Visits 10, 
14, 18, 22 and 26.
These visits are dosing 
visits and was missed 
from the original protocol. 
1.3 Schedule of Activities
Table 1-4: A window period of “1 
to 5 days postdose” for anti-
rozanolixizumab antibodies 
samples has been added to Week 13 
and Week 23. 
ADA postdose samples 
added to facilitate the 
clinical validation of drug 
tolerance in the ADA 
assay.
1.3 Schedule of Activities
Table 1-4: New footnote “j” was 
added and applied to vaccination 
titers. 
Added for further 
clarification on sample 
collection for the 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 214 of 220
Section # and Name
Description of Change
Brief Rationale
measurement of post-
vaccination titers.
1.3 Schedule of Activities
Footnotes corresponding to plasma 
complements (C3a and C5a) and 
blood sample for cytokines was 
changed from “s” to “t”
Error in original protocol.
1.3 Schedule of Activities
Table 1-4: IgA, IgM, IgE will be 
measured at Screening instead of 
Baseline. 
This is required due to the 
update of Section 5.2 
Exclusion criteria; 
Criterion #17.
1.3 Schedule of Activities
Table 1-4: IgG will be also be 
measured at Weeks 7, 11, 15, and 
19. 
These visits (weeks) were 
missed from the original 
protocol. IgG will be 
monitored at these visits 
at the time of evaluating 
the primary clinical 
endpoint.
1.3 Schedule of Activities
Table 1-4: Footnote “w” was added 
to physical fatigue instrument. 
Added as was missed 
from the original protocol.
1.3 Schedule of Activities
Table 1-4: Abbreviation list was 
amended to include SFU (Safety 
Follow-Up). 
Administrative update.
1.3 Schedule of Activities
Table 1-4: Additional footnote 
(now footnote q) was added to 
indicate PK and ADA blood 
sampling are to be taken predose, 
unless otherwise stated.
Added as was missed 
from the original protocol.
5.2 Exclusion criteria
Criterion #17 has been amended to 
include “or a measurement of IgA 
<50mg/dL at the Screening Visit”
To exclude patients with 
undiagnosed IgA 
deficiency.
5.2 Exclusion criteria
Criterion #20 was amended: to 
remove “N. meningitidis” and 
include reference to see Section 5.4, 
screen failures.
For further clarification of 
screening related 
activities.
5.2 Exclusion criteria
Criterion #32 was amended: 
Glomerular filtration rate (GFR) 
was changed from 60 ml/min/1.73 
m2 to 45ml/min/1.73 m2.
Revised following FDA 
advice to relax the 
inclusion criteria and 
enroll patients with 
moderate renal 
impairment.
5.4 Screen failures
The following wording has been 
added: Study participants who had 
protective titers after vaccination, 
but failed screening for other 
For further clarification of 
screening related 
activities and to avoid 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 215 of 220
Section # and Name
Description of Change
Brief Rationale
reasons can be rescreened without 
reassessing titers within one year of 
initial screening.
unnecessary 
investigations.
6 Study Treatments
Table 6-1: minor changes to the 
dosing instructions and storage 
conditions have been made. 
Updated to provide 
clarity.
6.2.1.1 Maintenance of 
study treatment blind
Minor typographical changes have 
been made.
Updated to provide 
clarity.
6.4.3 Rescue therapy
Wording on steroids was amended 
to replace “High dose steroid, and 
pulse steroids” with “Any 
systemically administered 
corticosteroids (above the 
background doses) for 
management of infusion 
reactions”
Per FDA request to 
include any systemic 
increase in corticosteroids 
dose above the Baseline 
dose can be regarded as 
rescue therapy.
7.1.3 Discontinuation of 
IMP due to other adverse 
events or medical 
condition
Formatting was amended to remove 
assigned numbering. 
Updated to provide 
consistency for the listed 
criteria.
7.1.4 Temporary IMP 
discontinuation
This section was amended to 
include the possibility of mock 
infusions, and the reference to 
Appendix 25 was moved to the end 
of the section. 
An additional criterion has been 
added: Thrombocytosis (platelet 
count of ≥400x109/L)
Updated to provide 
clarity.
Added as was missed 
from the original protocol 
and to ensure consistency 
throughout the protocol. 
8.2.1 Physical 
examination
Height and weight have been 
removed from the full physical 
examination.
Height and weight 
assessments will be 
performed separately and 
not part of the full 
physical examination.
8.2.6 Splenectomized 
study participants
New wording has been included: 
Splenectomized participants will be 
assessed again for vaccination titers 
at Screening (see Table 1-4).
For further clarification of 
screening related 
activities.
9.3.1 Analysis of the 
primary efficacy/primary 
endpoint
The measurement of a durable 
clinically meaningful platelet 
response was corrected from 
greater (“>”) to greater than or 
equal to (“≥”) 50x109/L.
New wording was added: “Missing 
platelet count at any visit will be 
Updated to correct a 
typographical error.
Per FDA request to 
include details on 
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 216 of 220
Section # and Name
Description of Change
Brief Rationale
considered "worst case" and set to 
zero ("no platelet response") for 
that specific visit.”
handling missing platelet 
count.
9.3.1 Analysis of the 
primary efficacy/primary 
endpoint
Table 9-1: The measurement of a 
platelet count was corrected from 
greater (“>”) to greater than or 
equal to (“≥”) 50x109/L.
Updated to correct a 
typographical error.
9.3.2 Analysis of the 
secondary efficacy 
endpoints
New wording has been included 
specific to the predefined order of 
formal hypotheses testing and the 
sequence they will be performed.
9.3.2 Analysis of the 
secondary efficacy 
endpoints
Table 9-2: an additional estimand 
for a secondary endpoint was added 
and minor typographical changes 
were made.
10.2 Appendix 2: Clinical 
laboratory tests
Table 10-1: Additional laboratory 
measurement and parameters were 
added. 
These laboratory 
measurements and 
parameters were missed 
from the original protocol.
10.4 Appendix 4: 
Contraceptive guidance 
and collection of 
pregnancy information
Wording specific to contraception 
guidance for male participants (first 
paragraph, first 3 bullet points, 
second paragraph, second bullet 
point) was removed. 
This information was not 
applicable to the study.
10.6 Appendix 6: Liver 
safety – suggested actions 
and follow-up 
assessments
Additional footnote (g) was added 
to follow-up assessments for 
bilirubin or INR: “These tests 
should be obtained when IgG levels 
are approaching normal levels 
because IMP may interfere with 
IgG levels and interpretation.”
Important to provide a 
timing for obtaining IgG 
samples due to 
interference of other tests.
10.8 Appendix 8: 
Country-specific 
requirements
The following changes have been 
made:
Moldova: Wording on the 
recommendation of the German 
Vaccination Recommendation 
Body has been removed, and 
reference to Table 1-3 has been 
added. 
Poland: A urine pregnancy test has 
been added at Week 27 (Visit 29) 
for sites located in Poland.
The additional urine pregnancy test 
on Day 29 has been removed.
The information specific 
to Moldova was no longer 
applicable to the study.
The updates to Poland 
were made to align with 
Polish Health Authority’s 
and Clinical Trial 
Facilitation Group 
recommendations.
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UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 217 of 220
Section # and Name
Description of Change
Brief Rationale
Appendix 15: Physical 
Fatigue Instrument
Minor typographical changes have 
been made.
Updated to be consistent 
with template form and 
provide clarity.
Appendix 17: PGI-S
Minor typographical changes have 
been made.
Updated to be consistent 
with template form and 
provide clarity.
Appendix 18: PGI-C
Minor typographical changes have 
been made.
Updated to be consistent 
with template form and 
provide clarity.
10.25 Appendix 25: 
New wording was added: Local 
guidelines regarding antibiotic 
prophylaxis in asplenic participant 
should be followed. Readily 
available antibiotics are encouraged 
for study participants.
To remind investigators 
about importance of 
antibiotic therapy in 
management of infections 
in Splenectomized 
patients.
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03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 218 of 220
11
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randomised controlled trial. Lancet. 2008;371(9610):395-403.
Lehmacher W and Wassmer G. Adaptive Sample Size Calculations in Group Sequential Trials. 
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McMillan R, Wang L, Tomer A, Nichol J, Pistillo J. Suppression of in vitro megakaryocyte 
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Oxford Textbook of Palliative Medicine, Oxford University Press. 1993;109.
PUBLIC COPY
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uman norm
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Drug Evalu
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ombopoie
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03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
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Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB, et al. International 
consensus report on the investigation and management of primary immune thrombocytopenia. 
Blood. 2010;115(2):168-86.
Rodeghiero F, Michel M, Gernsheimer T, Ruggeri M, Blanchette V, Bussel JB, et al. 
Standardization of bleeding assessment in immune thrombocytopenia: report from the 
International Working Group. Blood. 2013;121(14):2596-606.
Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, et al. Standardization 
of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults 
and children: report from an international working group. Blood. 2009;113(11):2386-93. 
Roopenian DC, Akilesh S. FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol. 
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munol.
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mary repo
naphylaxi
ons 
naphylaxi
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ep 2018;A
or v
ep 2018;A


UCB
03 Dec 2021
Clinical Study Protocol Amendment 3
Rozanolixizumab
TP0003
Confidential
Page 220 of 220
SPONSOR DECLARATION
I confirm that I have carefully read and understand this protocol and agree to conduct this 
clinical study as outlined in this protocol and according to current Good Clinical Practice.
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof. 

SAP_001.pdf: 
UCB 
 
16Aug2022 
Statistical Analysis Plan 
Rozanolixizumab 
TP0003 
 
 
 
 
 
 
Confidential 
Page 1 of 85 
 
TP0003 
STATISTICAL ANALYSIS PLAN 
 
AMENDMENT 3 
Study: TP0003 
Product: Rozanolixizumab 
 
A PHASE 3 MULTICENTER, DOUBLE-BLIND, RANDOMIZED, 
PLACEBO-CONTROLLED STUDY TO EVALUATE THE 
EFFICACY, SAFETY, AND TOLERABILITY OF 
ROZANOLIXIZUMAB IN ADULT STUDY PARTICIPANTS WITH 
PERSISTENT OR CHRONIC PRIMARY IMMUNE 
THROMBOCYTOPENIA (ITP)  
 
 
 
SAP/Amendment Number Date 
Final SAP 
10 Jul 2020 
SAP Amendment 1 
27 Jan 2021 
SAP Amendment 2 
22 Feb 2021 
SAP Amendment 3 
16 Aug 2022 
Confidentiality Statement  
Confidential 
This document is the property of UCB and may not – in full or in part – be passed on, 
reproduced, published, or otherwise used without the express permission of UCB. 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof. 


UCB 
 
16Aug2022 
Statistical Analysis Plan 
Rozanolixizumab 
TP0003 
 
 
 
 
 
 
Confidential 
Page 2 of 85 
 
TABLE OF CONTENTS 
1 
INTRODUCTION ........................................................................................................... 10 
2 
PROTOCOL SUMMARY ............................................................................................... 10 
2.1 
Study objectives ........................................................................................................... 10 
2.1.1 
Primary objective ................................................................................................. 10 
2.1.2 
Secondary objective ............................................................................................. 10 
2.1.3 
Exploratory objectives ......................................................................................... 10 
2.2 
Study endpoints ............................................................................................................ 11 
2.2.1 
Efficacy endpoints ............................................................................................... 11 
2.2.1.1 
Primary efficacy endpoint ......................................................................... 11 
2.2.1.2 
Secondary efficacy endpoints .................................................................... 11 
2.2.1.3 
Other efficacy endpoints ........................................................................... 11 
2.2.1.4 
Exploratory endpoints ............................................................................... 12 
2.2.2 
Safety endpoints ................................................................................................... 12 
2.2.2.1 
Other safety endpoints ............................................................................... 13 
2.3 
Study design and conduct ............................................................................................ 13 
2.4 
Determination of sample size ....................................................................................... 15 
3 
DATA ANALYSIS CONSIDERATIONS ...................................................................... 16 
3.1 
General presentation of summaries and analyses ........................................................ 16 
3.2 
General study level definitions .................................................................................... 17 
3.2.1 
Analysis time points ............................................................................................ 17 
3.2.1.1 
Relative day ............................................................................................... 18 
3.2.2 
Study periods ....................................................................................................... 18 
3.2.3 
Mapping of assessments performed at Early Withdrawal Visit .......................... 19 
3.2.4 
Dosing Regimen .................................................................................................. 19 
3.3 
Definition of Baseline values ....................................................................................... 19 
3.4 
Protocol deviations....................................................................................................... 19 
3.5 
Analysis sets................................................................................................................. 19 
3.5.1 
Enrolled Set (ES) ................................................................................................. 19 
3.5.2 
Randomized Set (RS) .......................................................................................... 19 
3.5.3 
Safety Set (SS) ..................................................................................................... 20 
3.5.4 
Full Analysis Set (FAS) ....................................................................................... 20 
3.5.5 
Pharmacodynamic Per-Protocol Set (PD-PPS) ................................................... 20 
3.5.6 
Pharmacokinetic Per-Protocol Set (PK-PPS) ...................................................... 20 
3.6 
Treatment assignment and treatment groups ............................................................... 20 
3.7 
Center pooling strategy ................................................................................................ 21 
3.8 
Coding dictionaries ...................................................................................................... 21 
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UCB 
 
16Aug2022 
Statistical Analysis Plan 
Rozanolixizumab 
TP0003 
 
 
 
 
 
 
Confidential 
Page 3 of 85 
 
3.9 
Changes to protocol-defined analyses ......................................................................... 21 
4 
STATISTICAL/ANALYTICAL ISSUES ....................................................................... 23 
4.1 
Adjustments for covariates/factors .............................................................................. 23 
4.2 
Handling of dropouts or missing data .......................................................................... 23 
4.2.1 
Handling missing data for the primary and secondary efficacy endpoints .......... 23 
4.2.2 
Missing Data due to COVID-19 .......................................................................... 23 
4.2.3 
Dates and times .................................................................................................... 23 
4.3 
Handling of repeated and unscheduled measurements ................................................ 26 
4.4 
Handling and definition of the Corticosteroid (CS) prednisone equivalent dose ........ 26 
4.5 
Interim analysis and data monitoring ........................................................................... 27 
4.5.1 
Data Monitoring ................................................................................................... 27 
4.6 
Multicenter studies ....................................................................................................... 28 
4.7 
Multiple comparisons/multiplicity ............................................................................... 28 
4.8 
Use of an efficacy subset of participants ..................................................................... 28 
4.9 
Active-control studies intended to show equivalence .................................................. 28 
4.10 
Examination of subgroups ........................................................................................... 28 
5 
STUDY POPULATION CHARACTERISTICS ............................................................. 28 
5.1 
Subject disposition ....................................................................................................... 28 
5.2 
Protocol deviations....................................................................................................... 29 
6 
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS ........................ 30 
6.1 
Demographics .............................................................................................................. 30 
6.2 
Other Baseline characteristics ...................................................................................... 31 
6.2.1 
Baseline disease characteristics ........................................................................... 31 
6.2.2 
Lifestyle ............................................................................................................... 32 
6.3 
Previous and ongoing medical history ......................................................................... 32 
6.4 
Procedure history and concomitant medical procedures ............................................. 32 
6.5 
Concomitant medications............................................................................................. 32 
6.5.1 
Assignment of medications to treatment period .................................................. 34 
6.6 
Prohibited concomitant medications and rescue medication ....................................... 34 
6.6.1 
Prohibited concomitant medication ..................................................................... 34 
6.6.2 
Rescue Therapy ................................................................................................... 35 
7 
MEASUREMENTS OF TREATMENT COMPLIANCE ............................................... 35 
8 
EFFICACY ANALYSES ................................................................................................ 35 
8.1 
Statistical analysis of the primary efficacy endpoint ................................................... 35 
8.1.1 
Primary analysis of the primary efficacy endpoint .............................................. 35 
8.2 
Statistical analysis of the secondary efficacy endpoints .............................................. 36 
8.2.1 
Cumulative number of weeks with Clinically Meaningful Platelet Response of 
≥50x109/L over the 24-Week treatment period (Week 1 to Week 25) ................ 36 
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8.2.2 
Time to first Clinically Meaningful Platelet Response of ≥50x109/L: time from 
starting treatment to achievement of first response of ≥50x109/L. ...................... 37 
8.2.2.1 
Definition ................................................................................................... 37 
8.2.2.2 
Estimand’s attributes ................................................................................. 37 
8.2.3 
Clinically Meaningful Platelet Response by Day 8, defined as platelet count 
≥50x109/L ............................................................................................................ 38 
8.2.4 
Response defined as platelet count ≥30x109/L and at least a 2-fold increase of 
the Baseline count confirmed on at least 2 separate occasions at two adjacent 
nominal visits at least 7 days apart, and absence of bleeding .............................. 38 
8.2.4.1 
Estimand’s attributes ................................................................................. 39 
8.2.4.2 
Sensitivity analysis .................................................................................... 39 
8.2.5 
Time to first rescue therapy ................................................................................. 39 
8.2.5.1 
Estimand’s attributes ................................................................................. 39 
8.2.6 
Change from Baseline to Week 25 in ITP-PAQ Symptom score ........................ 39 
8.3 
Statistical analysis of other efficacy endpoints ............................................................ 40 
8.3.1 
Cumulative number of weeks over the planned 24-Week treatment period with 
platelet counts ≥30×109/L and at least doubling from Baseline. ......................... 40 
8.3.2 
Mean change from Baseline in platelet count by visit ......................................... 40 
8.4 
Statistical analysis of exploratory endpoints ................................................................ 40 
8.4.1 
ITP Bleeding Score .............................................................................................. 40 
8.4.1.1 
ITP-specific Bleeding Assessment Tool (ITP-BAT) bleeding events and 
severity by visit ......................................................................................... 40 
8.4.1.2 
ITP bleeding at Screening ......................................................................... 41 
8.4.1.3 
Presence/Absence of ITP bleeding ............................................................ 41 
8.4.2 
Effect of Rozanolixizumab on Health-Related Quality of Life (HRQoL) .......... 41 
8.4.2.1 
European Quality of Life-5 Dimensions, 5 Levels (EQ-5D-5L) item 
responses ................................................................................................... 41 
8.4.2.2 
Short form 36-item (SF-36) domain and composite scores....................... 42 
8.4.2.3 
ITP-PAQ Domain Scores .......................................................................... 42 
8.4.3 
Hospitalization due to ITP / Number and length of hospitalizations ................... 43 
8.4.4 
Effect of Rozanolixizumab on Patient Reported Outcomes (PRO) ..................... 43 
8.4.4.1 
FATIGUE-PRO physical fatigue score ..................................................... 43 
8.4.4.2 
Patient Global Impression of Severity (PGI-S) ......................................... 43 
8.4.4.3 
Patient Global Impression of Change (PGI-C) .......................................... 43 
9 
PHARMACOKINETICS (PK) AND PHARMACODYNAMICS (PD) ........................ 43 
9.1 
Pharmacokinetics ......................................................................................................... 43 
9.2 
Antidrug antibodies (ADA) ......................................................................................... 44 
9.3 
Pharmacodynamic endpoints (PD) .............................................................................. 48 
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9.3.1 
Total serum IgG (absolute value) and change from Baseline (absolute value and 
percentage) in serum IgG and in serum IgG subclass concentration at each 
scheduled assessment ........................................................................................... 48 
9.3.2 
Serum immunoglobulin concentrations (IgA, IgE, IgM) at each scheduled 
assessment ............................................................................................................ 48 
9.4 
Influence of Rozanolixizumab on vaccination titers ................................................... 49 
9.4.1 
Vaccination titers against Streptococcus pneumoniae, Neisseria meningitidis, 
and Haemophilus influenzae in splenectomized study participants .................... 49 
9.4.2 
Percent change from Baseline in vaccination titers against tetanus in all study 
participants ........................................................................................................... 49 
10 SAFETY ANALYSES ..................................................................................................... 49 
10.1 
Extent of exposure ....................................................................................................... 49 
10.2 
Adverse events ............................................................................................................. 50 
10.2.1 
Data considerations .............................................................................................. 50 
10.2.2 
Adverse Event Summaries ................................................................................... 52 
10.3 
Vital Signs, Physical Findings, and Other Observations Related to Safety................. 53 
10.3.1 
Vital Signs and Physical Findings ....................................................................... 53 
10.4 
12-lead Electrocardiograms (ECG) .............................................................................. 54 
10.5 
Clinical Safety Laboratory Assessments ..................................................................... 54 
10.5.1 
Potential Drug-Induced Liver Injury ................................................................... 55 
10.6 
Concentrations of Total Protein and Albumin ............................................................. 55 
10.7 
Serum and Plasma Complement Levels ...................................................................... 56 
10.8 
Other Safety Variables ................................................................................................. 56 
10.8.1 
Physical examination ........................................................................................... 56 
10.8.2 
Pregnancy testing ................................................................................................. 56 
10.8.3 
Childbearing potential ......................................................................................... 56 
10.8.4 
Assessment and management of Tuberculosis .................................................... 56 
11 OTHER ANALYSES ...................................................................................................... 56 
11.1 
Specific analyses for Pharmaceuticals and Medical Devices Agency (PMDA).......... 56 
11.2 
Headache questionnaire ............................................................................................... 56 
12 REFERENCES ................................................................................................................ 56 
13 APPENDICES ................................................................................................................. 58 
13.1 
AE of focus (AEOF) for the Rozimab Program .......................................................... 58 
13.2 
Laboratory assessments – Marked abnormality criteria .............................................. 63 
13.2.1 
Hematology .......................................................................................................... 63 
13.2.2 
Chemistry ............................................................................................................. 64 
13.3 
Vital sign assessments - abnormal ............................................................................... 66 
13.4 
Electrocardiogram (ECG) – Abnormal ........................................................................ 66 
13.5 
ITP-PAQ Scoring ......................................................................................................... 67 
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13.5.1 
ITP-PAQ Scales ................................................................................................... 67 
13.6 
ITP bleeding score ....................................................................................................... 69 
13.7 
Classification of the SF-36v2 questionnaire ................................................................ 80 
14 AMENDMENT(S) TO THE STATISTICAL ANALYSIS PLAN (SAP) ...................... 81 
14.1 
AMENDMENT 3......................................................................................................... 81 
 
 
 
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LIST OF TABLES 
Table 2-1:  
Expected sample size ....................................................................................... 16 
Table 4-1: 
Calculation rules for duration of AEs .............................................................. 24 
Table 4-2: 
Prednisone equivalent doses of systemic corticosteroids/steroids ................... 27 
Table 6-1: 
Concomitant Medications Classification ......................................................... 34 
Table 8-1: 
Intercurrent Events (ICE), Intercurrent Events Strategies (ICES) and 
Missing data Strategies for the analysis of the primary endpoint .................... 36 
Table 8-2: 
Intercurrent Events (ICE), Intercurrent Events Strategies (ICES) and 
Missing data Strategies for the analysis of the Cumulative number of 
weeks with Clinically Meaningful Platelet Response of ≥50x109/L over 
the 24-Week treatment period .......................................................................... 36 
Table 8-3: 
Intercurrent Events (ICE), Intercurrent Events Strategies (ICES) and 
Missing data Strategies for the analysis of Time to first Clinically 
Meaningful Response of ≥50x109/L ................................................................ 37 
Table 8-4: 
Intercurrent Events (ICE), Intercurrent Events Strategies (ICES) and 
Missing data Strategies for the analysis of Clinically Meaningful 
Response by Day 8........................................................................................... 38 
Table 8-5: 
 Intercurrent Events (ICE), Intercurrent Events Strategies (ICES) and 
Missing data Strategies for the analysis of Time to first rescue therapy ......... 39 
Table 8-6: 
Intercurrent Events (ICE), Intercurrent Events Strategies (ICES) and 
Missing data Strategies for the analysis of cumulative number of weeks 
over the planned 24-Week treatment period with platelet counts 
≥30×109/L and at least doubling from Baseline.. ............................................ 40 
Table 8-7: 
ITP-specific Bleeding Assessment Tool (ITP-BAT) Domains and 
categories ......................................................................................................... 41 
Table 9-1: 
Terms and Definitions for ADA Status Evaluation in Study Participants ....... 46 
Table 10-1: 
TP0003 dose levels and weight tiers of rozanolixizumab ............................... 50 
Table 10-2: 
Laboratory criteria for PDILI........................................................................... 55 
Table 13-1: 
ITP-BAT scoring ............................................................................................. 70 
 
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List of Abbreviations 
 
ADAs 
Antidrug antibodies 
AEOF 
Adverse event of focus 
BLQ 
Below the limit of quantification 
BP 
Blood pressure 
CP 
Confirmed positive 
CSR               
Clinical Study Report 
CV                   
Coefficient of variation 
DEM 
Data Evaluation Meeting 
DNA 
Deoxyribonucleic acid  
ECG              
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EOS 
End of Study  
EQ-5D-5L 
European Quality of Life-5 Dimension 5 Level Assessment 
ES                   
Enrolled Set 
EudraCT        
European Union Drug Regulating Authorities Clinical Trials 
EW 
Early withdrawal  
FAS               
Full Analysis Set 
FDA 
Food and Drug Administration 
geoCV          
Geometric coefficient of variation 
geoMean        
Geometric mean 
hCG            
Human chorionic gonadotropin 
HLT             
High level term 
HRQoL 
Health-related quality of life 
ICH              
International Council for Harmonisation  
IDMC              
Independent Data Monitoring Committee 
IgA 
Immunoglobulin A 
IgG 
Immunoglobulin G 
IgM 
Immunoglobulin M 
IMP             
Investigational medicinal product 
IPD 
Important protocol deviations  
ITP              
Primary immune thrombocytopenia 
ITP-BAT       
ITP- Bleeding Assessment Tool 
ITP-PAQ 
ITP-Patient Assessment Questionnaire 
LLOQ          
Lower limit of quantification 
MCS 
Mental Component Summary 
MedDRA         
Medical Dictionary for Regulatory Activities 
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n                    
Number of participants 
NCP              
Not confirmed positive 
OLE 
Open Label Extension 
PCS 
Physical Component Summary 
PD               
Pharmacodynamic 
PDILI 
Potential drug-induced liver injury 
PGI-C 
Patient Global Impression of Change 
PGI-S 
Patient Global Impression of Severity 
PK               
Pharmacokinetic 
PK-PPS         
Pharmacokinetic Per Protocol Set 
PROs 
Patient reported outcomes 
PT                
Preferred term 
RNA 
Ribonucleic acid  
RLZ 
Rozanolixizumab 
SAP             
Statistical Analysis Plan 
SC                
Subcutaneous 
SD               
Standard deviation 
SF-36   
Short-Form 36-Item Health Survey 
SFU 
Safety Follow-up  
SOC           
System organ class 
SS               
Safety Set 
TEAE           
Treatment-emergent adverse event 
TEMA          
Treatment-emergent markedly abnormal 
TFLs          
Tables, figures and listings 
TPO 
Thrombopoietin 
TPO-RAs 
Thrombopoietin-receptor agonists  
ULN            
Upper limit of normal 
 
 
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1 
INTRODUCTION 
The purpose of this statistical analysis plan (SAP) is to provide all information that is necessary 
to perform the statistical analyses of the study TP0003, including the final analyses. It also 
defines the summary tables, figures and listings (TFLs) to be included in the final Clinical Study 
Report (CSR) according to the protocol.  
This SAP is based upon, and assumes familiarity with, the following documents: 
Protocol Amendment 3: 03 Dec 2021 and all previous protocol versions 
DMC Charter 2: 14 Jun 2021  
At the time this SAP, that is based on Protocol Amendment 3, was written, the sponsor had 
decided to terminate this study. No study participant was randomized under Protocol 
Amendment 3 and hence all analyses that are described in this SAP will be run on data from 
study participants that were randomized according to previous versions of the protocol. These 
study participants did all receive a starting dose of 
 equivalent rozanolixizumab and 
continued dosing on a bi-weekly basis. None of the study participants were switched to weekly 
dosing prior to termination of the study. 
If a future protocol amendment necessitates a substantial change to the statistical analysis of the 
study data, this SAP may be amended accordingly. The content of this SAP is compatible with 
the International Council for Harmonisation (ICH)/Food and Drug Administration (FDA) E9 
Guidance documents. 
UCB is the Sponsor and Parexel is the Contract Research Organization (CRO) for this study. 
Note: The terms Investigational Medical Product (IMP) and study medication are used 
interchangeably in this document. 
2 
PROTOCOL SUMMARY 
2.1 
Study objectives 
2.1.1 
Primary objective 
To demonstrate the clinical efficacy of rozanolixizumab in maintenance treatment in study 
participants with primary ITP. 
2.1.2 
Secondary objective 
To assess the safety and tolerability of rozanolixizumab     
2.1.3 
Exploratory objectives 
• To evaluate the clinical efficacy as measured by the ITP bleeding score  
• To assess the effect of rozanolixizumab on health-related quality of life (HRQoL)  
• To assess hospitalizations due to ITP 
• To assess the effect of rozanolixizumab on patient reported outcomes (PROs) 
• To assess the pharmacokinetics of rozanolixizumab administered by subcutaneous (sc) 
infusion 
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• To evaluate the incidence and emergence of antidrug antibodies (ADAs) of rozanolixizumab    
• To assess the pharmacodynamic (PD) effects of rozanolixizumab    
• To assess the influence of rozanolixizumab treatment on vaccination titers 
• To assess the effect of rozanolixizumab on response to vaccination in study participants who 
received COVID-19 vaccine 
2.2 
Study endpoints 
2.2.1 
Efficacy endpoints 
2.2.1.1 
Primary efficacy endpoint 
Durable Clinically Meaningful Platelet Response of ≥50x109/L for at least 8 out of 12 weeks 
during the last 12 weeks (Week 13 to 25) 
2.2.1.2 
Secondary efficacy endpoints 
• Cumulative number of weeks with Clinically Meaningful Platelet Response of ≥50x109/L 
over the 24-week treatment period  
• Time to first Clinically Meaningful Platelet Response of ≥50x109/L: time from starting 
treatment to achievement of first response of ≥50x109/L 
• Clinically Meaningful Platelet Response of ≥50x109/L by Day 8 
• Response defined as platelet count ≥30x109/L and at least a 2-fold increase of the Baseline 
count confirmed on at least 2 separate occasions at two adjacent nominal visits at least 7 days 
apart, and absence of bleeding by visita,b 
• Time to first rescue therapy 
• Change from Baseline to Week 25 in ITP Patient Assessment Questionnaire (ITP-PAQ) 
Symptoms Score 
Notes: 
a Absence of bleeding indicated by Grade 0 for all domains of the skin, mucosae, and organs 
(SMOG), or a Skin Grade of 0 or 1. 
 b Nominal visits are on-site visits where ITP bleeding scale assessment is performed. 
2.2.1.3 
Other efficacy endpoints 
• Duration of first Clinically Meaningful Platelet Response of ≥50x109/L: measured from 
achievement of first Response to loss of Response (loss of Response defined as platelet count 
<50x109/L) 
• Time to first Response: time from starting treatment to achievement of Response 
• Usage of rescue therapy (Yes/No) by visit 
• Complete Response (platelet count): defined as platelet count ≥100x109/L confirmed on at 
least 2 separate occasions at two adjacent nominal visits at least 7 days apart, and absence of 
bleeding by visit  
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• Cumulative number of weeks over the planned 24-Week treatment period with platelet 
counts of ≥100x109/L 
• Cumulative number of weeks over the planned 24-Week treatment period with platelet 
counts ≥30×109/L and at least doubling from Baseline 
• Mean change from Baseline in platelet count by visit 
• Clinically Meaningful Platelet Response of ≥50x109/L, for at least 4 out of 6 weeks during 
the last 6 weeks (Week 19 to 25) 
• Clinically Meaningful Platelet Response of ≥50x109/L, for at least 6 out of 8 weeks during 
the last 8 weeks (Week 17 to 25) 
2.2.1.4 
Exploratory endpoints 
• ITP-specific Bleeding Assessment Tool (ITP-BAT) bleeding events and severity by visit  
• Change from Baseline in European Quality of Life-5 Dimension 5 Levels (EQ-5D-5L) item 
responses  
• Change from Baseline in Short form 36-item (SF-36) domain and composite scores 
• Change from Baseline in the ITP-PAQ V1 domain Scores  
• Number and length of hospitalizations 
• Change from Baseline in FATIGUE-PRO Physical Fatigue Score by visit  
• Change from Baseline in Patient Global Impression of Severity (PGI-S)  
• Patient Global Impression of Change (PGI-C) at all available post-baseline assessments  
• Plasma concentration of rozanolixizumab  
• ADAs at each scheduled assessment 
2.2.1.4.1 
Exploratory pharmacodynamic endpoint: 
• Total serum IgG (absolute value) and change from Baseline (absolute values and percentage) 
in serum IgG and in serum IgG subclass concentration at each scheduled assessment  
• Absolute values and change from Baseline (absolute values and percentage) in serum 
immunoglobulin concentrations (IgA, IgE, IgM) at each scheduled assessment 
2.2.1.4.2 
Other exploratory endpoints 
• Percent change from Baseline in vaccination titers against Streptococcus pneumoniae, 
Neisseria meningitidis, and Haemophilus influenzae in splenectomized study participants 
• Percent change from Baseline in vaccination titers against tetanus in all study participants 
• Change in biomarkers of COVID-19 vaccine response over time 
2.2.2 
Safety endpoints 
Secondary Safety Endpoints: 
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• Occurrence of treatment-emergent adverse events (TEAEs) 
• Occurrence of TEAEs leading to withdrawal of investigational medicinal product (IMP) (ie, 
study discontinuation) 
2.2.2.1 
Other safety endpoints 
• Occurrence of serious TEAEs 
• Occurrence of treatment related TEAEs 
• Occurrence of adverse events of special monitoring (AESM) 
2.3 
Study design and conduct 
This is a Phase 3, multicenter, double-blind, randomized, placebo-controlled study with 
rozanolixizumab in study participants with persistent or chronic primary ITP defined as more 
than 3 months, or 12 months of duration, respectively, since diagnosis. 
The study participants will be male and female adults with persistent or chronic primary ITP, a 
platelet count measurement at Screening and at Baseline with an average of the two <30x109/L 
(no single count may be >35x109/L) and a documented history of low platelet count prior to 
Screening. 
The primary objective of TP0003 is to evaluate the clinical efficacy of rozanolixizumab as a 
maintenance treatment in participants with persistent or chronic primary ITP. 
The study will assess whether multiple sc infusions of rozanolixizumab will result in a durable 
Clinically Meaningful Platelet count increase of ≥50x109/L, for at least 8 out of 12 weeks during 
the last 12 weeks of the Treatment Period (Week 13 to 25). On Day 1 (Baseline Visit), study 
participants will be randomized 2:1 to receive a fixed-unit dose of rozanolixizumab 
 
 or placebo QW until Week 24, with randomization stratified by the degree of 
thrombocytopenia (platelet count < or ≥15x109/L) and history of splenectomy (yes or no). The 
last assessments prior to the SFU Visit will be done at Week 25. Study participants will be 
observed during the 8-week SFU Period after the final administered dose.  
Note: As all study participants for the analysis were enrolled under previous protocol versions, 
they were randomized to receive a fixed-unit starting dose of rozanolixizumab 
 
 or placebo. Following the initial dose, study participants were receiving a fixed unit 
dose 
 rozanolixizumab or placebo Q2W until Week 23.  
The total maximum study duration per study participant is up to 35 weeks, including a Screening 
Period (up to 4 weeks), a Dose Adaptation Period (12 weeks), a Maintenance Period (12 weeks) 
and an SFU Period (8 weeks after final dose administered). Splenectomized participants will be 
required to attend a Prolonged Screening Period prior to the Screening Visit in order to receive, 
if applicable, the required vaccinations, which will extend the total study duration by up to 20 
weeks. 
The eligibility of study participants to participate in the study will be determined during the 
Screening Period. Once eligibility is confirmed, the study participants will come to the site on 
Day 1 (Baseline Visit) and receive a single fixed-unit dose of rozanolixizumab or placebo 
administered sc (based on randomization). 
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Rozanolixizumab or placebo will be administered as a sc infusion with an infusion pump at a 
 
. A fixed-unit dose across different body weight tiers, as 
presented in Table 1-2 in the study protocol will be applied. 
 
  
The placebo arm will use 0.9% sodium chloride aqueous solution (physiological saline, 
preservative-free) for sc administration, matching the volumes of the rozanolixizumab arm. 
Dosing will be followed by a series of postdose study assessments on Day 1 through Day 169, 
with a subsequent SFU Period through Day 218. On dosing days, for the first 2 weeks, a 4-hour 
post-dose observation will be in place. Assuming the first 2 doses were well tolerated, on dosing 
days in Week 3, 4, and 5, a 1-hour post dose observation will be in place. Assuming the first 5 
doses were well tolerated, on subsequent weeks, a 15-minute post-dose observation will be in 
place. However, if the dose needs to be decreased due to a TEAE(s) or dose needs to be 
increased, post dose observation will be extended to 1 hour after the end of infusion for the next 
2 infusions. The post-dose observation time frame may be extended at the discretion of the 
investigator. These recommendations are applicable for dosing at site and at home. Approval 
from the investigator and sponsor is required prior to the start of home dosing.  
Note: All study participants for the analysis described in this SAP were enrolled under previous 
protocol versions and randomized to bi-weekly dosing. SFU Period was until Day 211. For the 
first three infusions, they were expected to stay at the study site for 4 hours after the end of 
infusion, and 2 hours after the IMP infusion for the remaining visits until W23. If needed, 
observation time at site could be extended for each study participant. 
In exceptional circumstances (eg, pandemic, hurricanes, etc) where study-specific investigations 
may not be conducted according to study protocol, contingency measures will be in place (see 
Section 8 in the study protocol for details). 
Approximately 150 study participants were planned to be screened at approximately 70 sites 
from North America, Europe and Asia to achieve the targeted number of approximately 60 
evaluable study participants randomized to weekly dosing.  
Note: Due to a strategic decision, the study was stopped early after 33 participants were 
randomized to bi-weekly dosing per previous protocol versions. Thus, no participants were 
randomized to weekly dosing in the study per Protocol Amendment 3. 
All study participants completing the Treatment Period (with or without the need for rescue 
therapy) and fulfilling the OLE study (TP0004) eligibility criteria will be allowed to enroll into 
TP0004. 
If study participants require rescue therapy during the Treatment Period (Week 1 to Week 25), 
they were allowed to receive commercially available rescue therapy (Section 6.4.3 in the study 
protocol). 
An external IDMC was established to review the safety data at predefined intervals and ad hoc as 
needed, should emerging safety concerns arise during the study. The first IDMC meeting for the 
review of safety data was planned to occur after approximately 15 participants had received 3 
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doses of IMP in TP0003 or TP0006. The study was to be put on hold if any of the following 
occurred: 
• The IDMC judges it necessary for medical or safety reasons and 
• The sponsor or its designee judges it necessary for medical, safety, regulatory, or any other 
reasons consistent with applicable laws, regulations and Good Clinical Practice. 
• Three study participants experience any SAE of same type within the first 15 study 
participants who have received 3 doses of IMP across TP0003 and TP0006, unless the SAE 
is clearly unrelated to the study drug.  After Protocol Amendment 3, this rule no longer 
applied. 
−  For US and Canada only: Three study participants experience any SAE within the first 15 
study participants who have received at least one dose of IMP across TP0003 and TP0006, 
unless the SAE is clearly unrelated to the study drug. 
The IDMC has the possibility to unblind the data. Details of the IDMC composition, processes, 
and responsibilities will be documented in the IDMC charter. It is intended to have one IDMC 
for both of the pivotal studies (TP0003 and TP0006), where the data will be presented unpooled, 
ie, data from each study will be reviewed separately. Key safety data may be pooled at the 
discretion of the IDMC for protection of all study participants if warranted. 
Based on feedback from the IDMC, weekly dosing was suggested and it was implemented in 
protocol amendment 3. Study participants being treated with the bi-weekly dosing regimen 
would switch to the weekly dosing regimen once protocol amendment 3 was approved at the 
respective study site. 
Note: No study participants were actually switched to weekly dosing or started on weekly dosing 
prior to the termination of the study.  
Additionally, a Safety Signal Detection Team performed rozanolixizumab program-wide 
aggregated safety data reviews at predefined intervals. 
2.4 
Determination of sample size 
Following Protocol Amendment 3, the sample size calculation was amended to reflect the 
primary objective of assessing the treatment effect on participants who were randomized to 
weekly infusions. To achieve the study objectives within the sample size cap of the original 2-
stage adaptive design, the futility assessment and option for a sample size re-assessment were no 
longer considered and the sample size calculation was amended as appropriate for a fixed 
parallel group design. 
The observed durable platelet response rates (platelet count ≥50×10⁹/L during 6 or more of the 
last 8 weeks of treatment), from Kuter et al (2008) in splenectomized participants were 38% 
(16/42) on active and 0% (0/21) on placebo. In non-splenectomized participants the rates were 
61% (25/41) and 5% (1/21), respectively. 
Using the true response rate of 0.45 versus 0.05, a sample size of 60 participants randomized in a 
2:1 ratio (ie, n=40 on rozanolixizumab and n=20 on placebo) receiving weekly infusions would 
provide >90% power to detect a statistically significant difference between treatment groups 
using Fisher’s Exact Test at an alpha level of 0.025 (1-sided).  
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By definition participants who dropout of the study are determined as nonresponders and are 
incorporated in the overall response rate. If the number of dropouts is greater than anticipated by 
10%, the impact on the rozanalixizumab response rate would mean that it would drop to a 
response rate of 0.4. In such cases, the study would still achieve >80% power if the overall 
response rate on placebo remains at 0.05. 
If the response rate on placebo was 0.1 rather than the anticipated 0.05, the rozanolixizumab rate 
would need to be >0.45 to achieve 80% and >0.5 to achieve 90% power. Table 2-1 provides 
power estimates for a fixed study design of n=60 participants in a 2:1 randomization ratio. 
Table 2-1:  
Expected sample size 
Scenario 
Placebo Response Rate of 0.05 
Placebo Response Rate of 0.1 
RLZ 
Placebo 
Powera 
RLZ 
Placebo 
Powera 
1 
0.30 
0.05 
56% 
0.30 
0.10 
32% 
2 
0.35 
0.05 
73% 
0.35 
0.10 
48% 
3 
0.40 
0.05 
85% 
0.40 
0.10 
63% 
4 
0.45 
0.05 
93% 
0.45 
0.10 
77% 
5 
0.50 
0.05 
97% 
0.50 
0.10 
87% 
6 
0.55 
0.05 
98% 
0.55 
0.10 
93% 
a  Power for a Parallel Group Design with N=60 in a 2:1 randomization test computed with 
Fisher’s exact test using NQuery Advisor 7.0. 
Note: Due to sponsor decision, the study was stopped early after 33 study participants were 
randomized to bi-weekly dosing per previous protocol versions. Thus, no study participants were 
randomized to weekly dosing in the study per Protocol Amendment 3 and all analyses will be 
conducted on the first 33 study participants who had bi-weekly dosing. 
3 
DATA ANALYSIS CONSIDERATIONS 
3.1 
General presentation of summaries and analyses 
Statistical analysis and generation of tables, figures, participant data listings, and statistical 
output will be performed using SAS® Version 9.4 or higher (SAS Institute, Cary, NC, USA).  
All tables and listings will use Courier New font size 9. 
Descriptive statistics will be displayed to provide an overview of the study results. For 
continuous variables, descriptive statistics will include number of participants with available 
measurements (n), mean, standard deviation (SD), the median, minimum, and maximum.  
For categorical variables, the number and percentage of participants in each category will be 
presented. Unless otherwise noted, the denominator for percentages will be based on the number 
of participants included in the respective analysis set. Participants with missing data can 
generally be accounted for using the following approaches: 
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• For summaries of demographics and Baseline characteristics: summarize percentages based 
on all participants in the analysis set and include a “Missing” category (corresponding to 
participants with missing data for the variable being summarized) as the last row in the list of 
categories being summarized.  
• For summaries of efficacy and safety variables, unless otherwise specified: summarize 
percentages based only on those participants with observed data for the variable being 
summarized. As the denominator may be different from the number of participants in the 
analysis set being considered, the denominator should be displayed in the table. The general 
format for displaying this will be “n/Nsub (%).” 
Unless otherwise noted, all percentages will be displayed to one decimal place. No percentage 
will be displayed for zero counts, and no decimal will be presented when the percentage is 100%.  
For the purpose of the tabulations the lower and upper confidence limits for the percentages will 
be truncated at 0 and 100% respectively. 
For PK concentrations, summary statistics will include geometric mean, geometric coefficient of 
variation (CV), 95% confidence intervals (CIs) for geometric mean, arithmetic mean, SD, 
median, minimum, and maximum. All summaries of PK variables will be based on the observed 
values. No imputation will be used. 
Decimal places for descriptive statistics will always apply the following rules: 
• “n” will be an integer 
• Mean, SD, and median will use one additional decimal place compared to the original data 
• CV [%] will be presented with one decimal place 
• Minimum and maximum will have the same number of decimal places as the original value. 
If no participants have data at a given time point, for example, then only n=0 will be presented. 
However, if n<3, present the n, minimum and maximum only. If n=3, n, mean, median, 
minimum and maximum will be presented only. The other descriptive statistics will be left blank. 
Derived variables in general will display the mean, SD and median to 1 more decimal place than 
the variables used in the derivation. If the number of decimal places reported in the raw data is 
varied, then use either the maximum raw number of reported decimal places or 3, whichever is 
the lowest, as a guide for the descriptive statistics.  
3.2 
General study level definitions 
3.2.1 
Analysis time points 
All data will be analyzed based on the visits identified per the Schedule of Activities in the 
protocol. 
Note: As no study participants were randomized under Protocol Amendment 3 the visit schedule 
and associated activities relate to those of earlier protocol versions. 
Mapping to visit windows will not be applied.  For Early Withdrawal visits refer to Section 3.2.3. 
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3.2.1.1 
Relative day 
Relative day for an event will be derived with the date of the first sc infusion of study drug as 
reference. 
Relative days for an event of measurement occurring before the date of first sc infusion will be 
prefixed with '-' and are calculated as follows: 
 
Relative Day = [(Event Date – Date of First Infusion)] 
The relative day for an event or measurement occurring on or after the reference date to the date 
of the last infusion is calculated as follows: 
 
Relative Day = [(Event Date - Date of First Infusion) + 1] 
For events or measurements occurring after the date of the last sc infusion, relative day will be 
prefixed with ‘+’ in the data listings and will be calculated as follows: 
 
Relative Day = [(Event Date – Date of Last Infusion)] 
There is no relative Day 0. Relative day is not calculated for partial dates in cases where relative 
day is shown in a participant data listing. In such cases, relative day should be presented as ‘- -’ 
in the participant data listings. 
3.2.2 
Study periods 
The following study periods are defined for this trial: 
• Prolonged Screening Period: splenectomized participants will be required to attend a 
Prolonged Period prior to the Screening Visit for the assessment of vaccination titers and to 
receive, if applicable, the required vaccinations, which will extend the total study duration by 
up to 20 weeks. 
• Screening Period (up to 4 weeks): Starts at the time of the informed consent date and ends 
the day before the first dose administration of study drug (i.e. generally the day before Day 1 
visit date).  
Note: after signing the ICF splenectomized participants will go first through the Prolonged 
Screening Period and then to the Screening Period, while the non-splenectomized will go 
directly to the Screening Period. 
• Dose Adaptation Period (12 weeks): Starts on the day of the first dose administration of 
study drug (Day 1) and ends after the Week 13 visit assessments.  
• Maintenance Period (12 weeks): Starts on the day after the 12-week Dose Adaptation Period 
(Week 13) and ends after the Week 25 visit assessments (or at the Early Withdrawal (EW) 
Visit for study participants withdrawn from the study before Week 25 visit).  
• Treatment Period: Starts on the day of the first dose administration of study drug (Day 1) and 
ends after the Week 25 visit assessments (or at the EW Visit for study participants withdrawn 
from the study before Week 25 visit). It is the combination of the Dose Adaptation Period 
and the Maintenance Period. 
• Safety Follow-up Period (SFU): Starts with last dose administered and ends 8 weeks after 
final dose administered. 
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A study participant is considered to have completed the study if he/she has completed all phases 
of the study including the SFU Period or has successfully been enrolled (completed Visit 1 in 
TP0004) into TP0004 at Week 25. 
A study participant will be said to have completed the SFU period if she/he had completed the 
last scheduled visit in the SFU period. 
Study participants will have an EOS Visit performed 8 weeks after the final dose of IMP (unless 
they are enrolling in TP0004 at Week 25), or upon discontinuation of the study. 
3.2.3 
Mapping of assessments performed at Early Withdrawal Visit 
Early Withdrawal assessments will be assigned to the next scheduled site visit (following the last 
scheduled visit that the participant completed prior to EW) where each assessment is evaluated 
as per protocol. This approach means that there is a chance that EW data will be mapped to 
different visits according to the schedule of assessments.   
3.2.4 
Dosing Regimen 
Because no participants in TP0003 were randomized or treated under Protocol Amendment 3.0, 
analysis by dosing regimen will not be performed. 
3.3 
Definition of Baseline values 
Baseline will be the last available pre-dose value prior to the first infusion of study drug in the 
Treatment Period, or if missing, the Screening value. Scheduled or unscheduled measurements 
can be used as the Baseline value. If an unscheduled measurement occurs after the planned 
baseline measurement time point but before dosing, then the unscheduled measurement will be 
used. 
3.4 
Protocol deviations 
Important protocol deviations are deviations from the protocol which potentially could have a 
meaningful impact on study conduct or on the primary efficacy, key safety, or PK/PD outcomes 
(if applicable) for an individual participant. The criteria for identifying important protocol 
deviations will be defined within the appropriate protocol-specific document. Important protocol 
deviations will be reviewed as part of the ongoing data cleaning process and data evaluation. All 
important protocol deviations will be identified and documented prior to unblinding to confirm 
exclusion from the Pharmacokinetic Per-Protocol Set analysis set.  
3.5 
Analysis sets 
3.5.1 
Enrolled Set (ES) 
All study participants who have signed the informed consent. 
3.5.2 
Randomized Set (RS) 
The RS will include all enrolled study participants who were randomized. This is equivalent to 
the Intent-to-Treat Set. 
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3.5.3 
Safety Set (SS) 
The SS will include all randomized study participants who received at least one dose of IMP 
(partial or full). Analysis of this set will be according to the treatment the participants received 
and will be used for the demographic and safety analyses. 
3.5.4 
Full Analysis Set (FAS) 
The FAS consists of all randomized study participants who have received at least one sufficient  
sc infusion of IMP, have a valid Baseline, and at least 1 valid post-Baseline platelet count 
measurement during Weeks 13-25. 
Note: Due to the early termination of the study and changes to the analysis, the Full Analysis Set 
will not be included in the analysis and the clinical study report. 
3.5.5 
Pharmacodynamic Per-Protocol Set (PD-PPS) 
The PD-PPS is a subset of the SS, consisting of those study participants who had no important 
protocol deviations potentially affecting the serum concentration of total IgG, as confirmed 
during a pre-analysis review of the data prior to database lock. Protocol deviations may not 
necessarily lead to total exclusion of a participant from the PD-PPS but may lead to exclusion of 
specific data. 
Note: Due to the early termination of the study and changes to the analysis, the PD-PPS will not 
be included in the analysis and the clinical study report. 
3.5.6 
Pharmacokinetic Per-Protocol Set (PK-PPS) 
The PK-PPS is a subset of the SS, consisting of those study participants who received at least 
1 dose (as described above), had at least 1 valid PK measurement and no important protocol 
deviations affecting the PK variable, as confirmed during a pre-analysis review of the data prior 
to database lock. 
3.6 
Treatment assignment and treatment groups 
If after unblinding it is determined that participants at any time received incorrect treatment from 
their randomized assignment, then for safety analyses these participants will be reallocated to the 
appropriate treatment group. For example, if participants randomized to placebo received 
rozanolixizumab, then for the safety analyses, these participants will be reallocated to 
rozanolixizumab.  
Participants randomized to rozanolixizumab will only be reallocated to the placebo treatment 
group if they never received rozanolixizumab.  
Efficacy data will be summarized by randomized treatment group as shown below:  
• Placebo  
• RLZ 
Safety data will also be summarized based on the two groups and dose will not be shown in the 
header. Dose will be captured in the listings. 
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3.7 
Center pooling strategy 
It is planned to recruit participants in North America, Europe, and Asia in this study, with 
possible extension to other regions and countries. The data from all sites will be pooled for 
analysis purposes. 
3.8 
Coding dictionaries 
Adverse events (AEs) will be coded using version 24.0 or later of the Medical Dictionary for 
Regulatory Activities (MedDRA®).  
Medications will be coded according to version Mar 2021 or later of the World Health 
Organization Drug Dictionary (WHODD). Medical procedures will not be coded. 
3.9 
Changes to protocol-defined analyses 
(1) Analysis sets 
   (1.2) The FAS was removed from analysis 
   (1.3) The PD-PPS was removed from analysis 
(2) Added COVID-19 as an intercurrent event to all endpoints 
(3) Note: The study was terminated early after 33 participants were randomized to bi-weekly 
infusions per Protocol Amendment 2; no participants were randomized to weekly infusions in the 
study per Protocol Amendment 3. 
(4) No formal statistical analyses of efficacy endpoints were conducted. Only the primary and 
secondary efficacy endpoints were summarized descriptively and listed. Protocol-defined 
analyses for efficacy endpoints are described below. 
The primary efficacy analysis of the study was planned to conduct a Stratified Cochran-Mantel-
Haenszel test statistic. Sensitivity, supplemental and subgroup analyzes were planned to test the 
robustness of the assumption. The secondary efficacy analyses were planned to conduct a 
sequential hierarchical test procedure to protect the overall significance level for the multiplicity 
of endpoints. 
Primary and secondary efficacy endpoints listed below will be listed and summarized 
descriptively for study participants randomized to bi-weekly dosing according to previous 
protocol versions. 
• Durable Clinically Meaningful Platelet Response of ≥50x109/L for at least 8 out of 12 weeks 
during the last 12 weeks (Week 13 to 25) 
• Cumulative number of weeks with Clinically Meaningful Platelet Response of ≥50x109/L 
over the 24-week treatment period (Week 1 to Week 25) 
• Time to first Clinically Meaningful Platelet Response of ≥50x109/L: time from starting 
treatment to achievement of first response of ≥50x109/L 
• Clinically Meaningful Platelet Response of ≥50x109/L by Day 8 
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• Response defined as platelet count ≥30x109/L and at least a 2-fold increase of the Baseline 
count confirmed on at least 2 separate occasions at two adjacent nominal visits at least 7 days 
apart, and absence of bleeding by visit 
• Time to first rescue therapy 
• Change from Baseline to Week 25 in ITP Patient Assessment Questionnaire (ITP-PAQ) 
Symptoms Score 
Other efficacy endpoints listed below will be listed and summarized descriptively as well. 
• Cumulative number of weeks over the planned 24-Week treatment period with platelet 
counts ≥30×109/L and at least doubling from Baseline 
• Mean change from Baseline in platelet count by visit 
The data collected for all other efficacy endpoints will be listed only. 
(5) All sensitivity and supplemental analysis to the primary endpoint and to the secondary 
efficacy endpoints will not be performed 
(6) Subgroup analyses to the primary efficacy analysis will not be performed 
(7) Analysis for the PMDA on the Japanese subset of participants will not be performed 
(8) Change from baseline will not be calculated for the following endpoints. Only item responses 
will be listed. 
• Change from Baseline in European Quality of Life-5 Dimension 5 Levels (EQ-5D-5L) item 
responses  
• Change from Baseline in Short form 36-item (SF-36) domain and composite scores 
• Change from Baseline in the ITP-PAQ V1 domain Scores 
• Change from Baseline in FATIGUE-PRO Physical Fatigue Score by visit  
• Change from Baseline in Patient Global Impression of Severity (PGI-S) 
(9) Percent change from Baseline will not be calculated for the following endpoint. Titers will be 
listed. 
• Percent change from Baseline in vaccination titers against Streptococcus pneumoniae, 
Neisseria meningitidis, and Haemophilus influenzae in splenectomized study participants 
(10) The following endpoint will not be analyzed because no samples were collected: 
• Change in biomarkers of COVID-19 vaccine response over time 
(11) Change from Baseline will not be calculated for the following safety endpoints. Only raw 
data will be listed. 
• Vital signs change from Baseline (blood pressure [BP], pulse rate, body temperature) at each 
scheduled assessment during Treatment and SFU Periods 
• 12-lead echocardiogram (ECG) change from Baseline at each scheduled ECG visit 
• Laboratory change from Baseline (hematology including coagulation parameters, clinical 
chemistry, and urinalysis) at each scheduled assessment during Treatment and SFU Periods  
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• Change from Baseline in concentrations of total protein and albumin 
• Change from Baseline in serum complement levels (C3 and C4) and plasma complement 
levels (C3a and C5a) at each scheduled assessment during the study (for study participants 
experiencing infusion reactions or hypersensitivity reactions) 
• Absolute values and change from Baseline (absolute values and percentage) in serum 
immunoglobulin concentrations (IgA, IgE, IgM) at each scheduled assessment 
4 
STATISTICAL/ANALYTICAL ISSUES 
4.1 
Adjustments for covariates/factors 
No statistical analysis will be performed adjusting for covariates/factors. 
4.2 
Handling of dropouts or missing data 
4.2.1 
Handling missing data for the primary and secondary efficacy endpoints 
Study participants who have not met the threshold for clinically meaningful response will be 
imputed as non-responders for the analysis. Missing platelet data at any visit will be considered 
"worst case" and set to zero ("no response") for that specific visit. 
Missing data for ITP Patient Assessment Questionnaire (ITP PAQ) instrument will not be 
imputed.  
Missing efficacy data encountered due to permanent treatment discontinuation due to TEAEs, or 
the receipt of rescue therapy will be considered as intercurrent events. For the primary efficacy 
analysis, patients with intercurrent events will be considered as non-responders. 
Missing data strategy for PRO related endpoints will follow instructions indicated in each 
instrument. 
4.2.2 
Missing Data due to COVID-19  
Unless specified otherwise, study participants who have visits impacted by COVID-19 for any 
reason will be considered non-responders at the corresponding visit, and missing platelet count 
data due to COVID-19 will be considered worst case and set to zero (“no response”) for that 
particular visit. 
4.2.3 
Dates and times 
Partially and completely missing dates may be imputed for the following reasons: 
• Classification of Adverse events (AEs) as treatment-emergent 
• Classification of medications as past, prior, or concomitant 
• Durations of AEs. 
Imputed dates will not be shown in listings.  All dates will be displayed as reported in the 
database. 
The following rules will be applied for partial start dates: 
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• If only start month and year are specified and are not the same as month and year of first 
dosing, then use the 1st of the month  
• If only the month and year are specified and the month and year of first dosing is the same as 
the month and year of the start date, then use the date of first dosing. If this results in an 
imputed start date that is after the specified end date, then use the 1st of the start month, or 
the date of screening if this is later (if the latter imputation results in an end date that is 
earlier than the start date, then use the 1st of the month).  
• If only the year is specified, and the year of dosing is not the same as the year of the start date 
then use January 01 of the year of the start date.  
• If only the year is specified, and the year of dosing is the same as the year of the start date, 
then use the date of first dosing. If this results in an imputed start date that is after the 
specified end date, then use January 01 of the year of the start date, or the date of screening if 
this is later (if the latter imputation results in an end date that is earlier than the start date, 
then use January 01).  
• If the start date is completely unknown, then use the date of first dosing. If this results in an 
imputed start date that is after the specified end date, then use January 01 of the year of the 
end date, or the date of screening if this is later (if the latter imputation results in an end date 
that is earlier than the start date, then use January 01).  
Any medication with a start date on the first dosing date, will be assumed to be concomitant. 
The following rules will be applied for partial stop dates: 
• If only the month and year are specified, then use the last day of the month 
• If only the year is specified, then use December 31 of the known year 
If the stop date is completely unknown, do not impute the stop date, except for ITP medications 
where end date is missing and ongoing is ticked as “no”, which will be imputed as “Past” 
medications. 
Imputed AE dates will be used for the calculation of duration of AEs as described in Table 4-1. 
Table 4-1: 
Calculation rules for duration of AEs 
Data 
availability 
Onset date 
Outcome 
date 
Calculation rules 
Complete data 
Analysis 
Start Date 
(D1) 
Analysis 
End Date 
(D2) 
Duration = D2 – D1 + 1 day                
Start date 
partially or 
completely 
missing 
-- 
D2 
Duration = < D2 – D0 + 1 day              
Notes: D0 = imputed dose start date per partial stop dates.  
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Data 
availability 
Onset date 
Outcome 
date 
Calculation rules 
End date 
partially or 
completely 
missing 
D1 
-- 
If end date is completely missing, then: 
For ongoing AE  
Duration ≥ (Discharge day – D1) + 1 day or 
Duration ≥ (Data cut-off day – D1) + 1 day 
For resolved AE: 
Duration ≤ (Discharge day – D1) + 1 day  or 
Duration ≤ (Data cut-off day – D1) + 1 day  
 
Note: Where discharge refers to the date when the 
participant rolls over TP0004, or the date of EOS visit  
for study completers, or date of discontinuation for 
participants that were withdrawn from the study. 
 
If end date is partially missing, then: 
Duration = D3  - D1 + 1 day, where D3 is imputed end 
date using partial stop dates (see above). 
 
For any AEs with known start date, if the end date is 
missing, the date of last contact will be used as the 
discharge day. 
For participants still ongoing in the study at the time of 
the data cut-off, and for whom no discharge date is 
available, the date of the data cut-off will be used instead 
of the discharge date. 
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Data 
availability 
Onset date 
Outcome 
date 
Calculation rules 
Start and end 
date partially or 
completely 
missing 
-- 
-- 
For ongoing AE: 
Duration ≥ (Discharge day – D0) + 1 day  or 
Duration ≥ (Data cut-off day – D0) + 1 day   
 
For resolved AE: 
Duration ≤ (Discharge day – D0) + 1 day  or 
Duration ≤ (Data cut-off day – D0) + 1 day   
 
For a participant in the SS, D0 is the date of first 
administration of IMP, and for screen failures, D0 is the 
date of the screening visit. 
Note: Discharge refers to the date of the end of study 
visit or the date of discontinuation from the study for 
participants that withdraw. 
For any AEs with known start date if the end date is 
missing, the date of last contact will be used as the 
discharge day. 
For participants still ongoing in the study at the time of 
the data cut-off, and for whom no discharge date is 
available, the date of the data cut-off will be used instead 
of the discharge date.  
4.3 
Handling of repeated and unscheduled measurements 
All repeated and unscheduled measurements will be presented in the listings, where applicable. 
The following general rules will apply to all repeated and unscheduled measurements: 
• For repeated or unscheduled measurements obtained prior to the first dose of IMP the latest 
reliable value (which may be scheduled or unscheduled) will be used in the calculation of 
descriptive statistics (ie, Screening and/or Baseline) 
• For repeated or unscheduled measurements obtained at the designated Baseline visit, the 
latest reliable value (which may be scheduled or unscheduled) will be defined as the Baseline 
record if occurred prior to the first dose of IMP 
• If any scheduled measurement obtained at any time point after the first dose of IMP is 
missing, unscheduled measurements will not be used for any missing assessment. 
• See Section 10.4 for the rules applied to ECG triplicate measurements. 
4.4 
Handling and definition of the Corticosteroid (CS) prednisone 
equivalent dose 
For the purposes of further analysis and tabulations, all corticosteroid doses (including both prior 
and concomitant corticosteroids taken for any indication) will be converted to prednisone 
equivalent doses. The conversion table for systemic corticosteroids is presented in Table 4-2. 
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Systemic corticosteroids are those with a route of administration of oral, intravenous, or 
intramuscular. All others (including topical, ocular, nasal, subcutaneous, intraarticular, etc.) will 
be considered non-systemic steroids which will have a prednisone equivalent dose = 0mg/day. 
Budenoside is considered non-systemic even if taken orally and will always be assigned a 
prednisone equivalent dose = 0mg/day.  
The prednisone equivalent dose will be included in the listing.  
For example, if the total daily dose of triamcinolone is 8mg, the equivalent total daily dose of 
prednisone will be 10mg. If a new corticosteroid is reported that is not in Table 4-2, the 
appropriate prednisone equivalent conversion will be determined and the prednisone equivalent 
dose will be included in a separate systemic corticosteroids concomitant medication listing. 
If medications are available in 
 which are not in table below, then the dose 
equivalent to 5mg/day Prednisone will be provided by the physician for this new system CS and 
the TFL footnote will be updated with this information for the newly identified CS 
Table 4-2: 
Prednisone equivalent doses of systemic corticosteroids/steroids   
Corticosteroids /Steroids 
Dose equivalent to  
5mg/day Prednisone 
Cortisone  
25 
Hydrocortisone  
20 
Deflazacort  
6.5 
Prednisone  
5 
Prednisolone 
Methylprednisolone  
5 
4 
Triamcinolone  
4 
Dexamethasone  
0.75 
Betamethasone  
0.6 
Notes:  
− 
All non-systemic corticosteroids (including topical, ocular, nasal, subcutaneous, intra articular, etc.) will be 
assigned a prednisone equivalent dose = 0 mg/day.  
− 
ATC2 Term = "CORTICOSTEROIDS FOR SYSTEMIC USE, 
" 
4.5 
Interim analysis and data monitoring 
4.5.1 
Data Monitoring  
An external IDMC will be established to review the safety data at predefined intervals and ad 
hoc as needed, should emerging safety concerns arise during the study. The IDMC will consist of 
members independent from UCB. Study enrollment will not be halted during planned IDMC 
review of the safety and efficacy data. The IDMC will have the possibility to unblind the data. 
Details of the IDMC composition, processes, and responsibilities will be documented in the 
IDMC charter. One IDMC is planned for both pivotal studies (TP0006 and TP0003), where the 
safety data will be initially presented unpooled, ie, data from each study will be reviewed 
separately. Key safety data may be pooled at the discretion of the IDMC for protection of all 
study participants if warranted. The first IDMC meeting for the review of safety data is planned 
to occur after approximately 15 participants have received 3 doses of IMP in TP0003. The 
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intervals for planned IDMC meetings are included in the section 4.1.2.1 in the TP0003/TP0006 
Independent Data Monitoring Committee Charter. The study will be put on hold if any of the 
following occurs: 
• The IDMC judges it necessary for medical or safety reasons and 
• The sponsor or its designee judges it necessary for medical, safety, regulatory, or any other 
reasons consistent with applicable laws, regulations and Good Clinical Practice. 
• An ad hoc IDMC meeting for the review of safety data is planned to occur if one of the 
stopping rules is met: 
− US & Canada Rule: Three participants experience any serious adverse event (SAE) 
within the first 15 study participants who have received at least one dose of IMP across 
TP0003 and TP0006, unless the SAE is clearly unrelated to the study drug. 
− Rest of World Rule: Three participants experience an SAE of the same type within the 
first 15 study participants who have received 3 doses of IMP across TP0003 and TP0006, 
unless the SAE is clearly unrelated to the study drug. 
4.5.2  
Interim analyses: 
The interim analysis planned for this study under previous protocol versions was removed from 
Protocol Amendment #3. 
4.6 
Multicenter studies 
This is a multicenter study however individual center’s results will not be presented.  
4.7 
Multiple comparisons/multiplicity 
As inferential statistical analyses will no longer be performed this section is not applicable. 
4.8 
Use of an efficacy subset of participants 
Subset analyses will no longer be performed. 
4.9 
Active-control studies intended to show equivalence 
Not applicable 
4.10 
Examination of subgroups 
Subgroups will no longer be examined. 
5 
STUDY POPULATION CHARACTERISTICS 
5.1 
Subject disposition 
The following outputs will be created. 
Summaries: 
− Reasons for screen failures (as collected on the Study Termination Screen Failure CRF 
page) will be summarized using the ES for overall for all screened study participants who 
failed to be randomized. 
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−
Disposition of study participants screened will be summarized using the ES for overall,
by region and by site. In this summary, the site number, principal investigator name, first
subject in date, last subject out date, will be captured by randomized treatment, and by
each analysis set (ES, RS, SS, PK-PPS).
−
Disposition of Analysis Sets: summary of disposition of study participants by treatments
group, by analysis sets (ES, RS, SS, and PK-PPS) using the RS.
−
Disposition and Discontinuation Reasons, using the RS, will contain the number and
percentage of study participants who:
o
Started study and started each study period (Dose Adaptation Period,
Maintenance Period and SFU Period)
o
Completed the study and completed each study period study period (Dose
Adaptation Period, Maintenance Period and SFU Period)
o
Discontinued study and discontinued in each study period (Dose Adaptation
Period, Maintenance Period and SFU Period)
o
Primary Reason for discontinuation (premature study termination as collected in
the Study Termination CRF)
−
Discontinuation due to AEs, using the RS to tabulate the total number of study
participants who discontinued the study due to AEs by treatment group, and the
categories: AE serious, fatal, AE non-fatal and other (AE non-serious, fatal).
-
COVID-19 Disposition:  Disposition and discontinuation reasons using the RS will
contain the number and percentage of study participants who started, completed and
permanently discontinued Treatment Period / Observation Period overall and by pre-, and
during the COVID-19 pandemic based on the start, completed and discontinuation date
relative to the pandemic cut-off date. The pandemic start date is March 20, 2020.  The
discontinuation reason in each period will also be summarized. Discontinuation due to
COVID-19 pandemic will be listed as sub-category under “Other” reason.
5.2 
Protocol deviations 
Important Protocol deviations will be summarized by treatment group, using the RS to include 
the number and percentage of participants with: 
a.
No important protocol deviations
b. At least one important protocol deviation and the
−
Inclusion criteria deviation
−
Exclusion criteria deviation
−
Withdrawal criteria deviation
−
Prohibited concomitant medication use
−
Incorrect treatment or dose
−
Treatment non-compliance
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− Procedural non-compliance 
c. Number of Participants excluded from the PK-PPS (and all categories in item b above). 
d. A summary of number and percentage of participants with an important protocol deviation 
by relationship to COVID-19 and treatment group will be provided for the RS. Additionally, 
the summary will be repeated by pre- and during the COVID-19 pandemic based on the 
deviations start date relative to the pandemic cut-off date. The pandemic start date is March 
20, 2020.   
A by-study participant listing of important protocol deviations will be provided using the RS. 
Note:  The criteria for exclusion of study participants and/or study data from the PK-PPS will be 
defined in the Protocol Deviation Specification document. 
6 
DEMOGRAPHICS AND OTHER BASELINE 
CHARACTERISTICS 
Unless otherwise specified, all summaries will be based on the RS.  
6.1 
Demographics 
Demographic variables will be summarized on the RS, by categories mentioned below using 
descriptive statistics, by treatment group and overall.   
Categories for continuous variables (including n, mean, SD, Median, Min and Max): 
• Age (years) - at the time of study entry. 
• Weight (kg) 
• Height (cm) 
• BMI (kg/m2) calculated as: 𝐵𝑀𝐼= 
Weight (kg)
(Height (m))2 
Categorical variables (using frequency counts and percentages): 
• Age (18 - <65, 65 - <85, ≥85 years) 
• Age (≤18, 19 - <65, ≥65 years)  
• BMI (<25, 25 to <30, ≥30 kg/m2) 
• Weight (<50kg, 50kg-<70 kg, 70-<100kg, ≥100kg) 
• Gender (Male, Female) 
• Race (American Indian or Alaska native, Asian, Black, Native Hawaiian or Other Pacific 
Islander, White, Other/Mixed) 
• Ethnicity (Hispanic or Latino, Not Hispanic or Latino) 
• Region (North America, Europe, Asia [excluding Japan], Japan) 
• Country 
By-study participant listings of demographics will be provided.  
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Childbearing potential will be listed for the RS. 
6.2 
Other Baseline characteristics 
6.2.1 
Baseline disease characteristics  
Baseline disease variables will be summarized using the RS, using descriptive statistics by 
treatment group and overall: 
• Age at first ITP diagnosis (years) 
• Time since first confirmed diagnosis of ITP (as collected in the eCRF) 
• Splenectomy (Yes/No) 
• IgG level (g/L) for 
− Non-splenectomized participants 
− Splenectomized participants 
• Platelet count (x109/L) (as collected in the eCRF) 
• Degree of thrombocytopenia (platelet count < or ≥15x109/L) (using data collected in the 
eCRF)  
• ITP Duration (persistent or chronic primary ITP as defined in Section 2.3) 
• Total number of prior unique ITP medications (continuous) 
• Total number of prior ITP medications (continuous) 
• Number of prior unique ITP medications (1, 2 and ≥3)  
• Concomitant use of TPO-RAs (eg,  Eltrombopag and/or Avatrombopag) (Yes/No) 
Notes: 
− Persistent or chronic primary ITP as defined in Section 2.3 
− In addition, the number and percentages of study participants in each stratum for each 
stratification factor (splenectomy (yes/no), degree of thrombocytopenia (platelet count < 
or ≥15x109/L) will be presented.  
− Data will be summarized using data captured or derived from eCRF. 
− The duration of ITP for chronic ITP participants will be computed in years and it will be 
calculated as follows: 
Date of Screening – Date of Diagnosis
365.25
 , where the date of diagnosis will be obtained from the ITP 
history eCRF page. 
− The duration of ITP – for persistent ITP participants will be computed in months and it 
will be calculated as: 
Date of Screening – Date of Diagnosis
30.5
 , where the date of diagnosis will be obtained from the ITP 
history eCRF page.  
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− Age at diagnosis (years) will be calculated as: 
Date of first diagnosis − Date of birth
365.25
 
− If the date of diagnosis is missing, the duration of disease and age at first diagnosis will 
not be calculated. In the case of the day (of the date of first diagnosis) being missing, then 
the day will be imputed with the last of the month. In the case day and month being 
missing (for the date of first diagnosis), the date will be imputed with 31st December. 
Note:  if the imputation results in an imputed diagnosis date that is after screening date, 
then the diagnosis date will be imputed to the screening date. 
− The duration of ITP will be presented in the listings as follows: 
◦ 
In years to 1 decimal place for chronic primary ITP participants 
◦ 
In months (3-12) for persistent primary ITP participants 
− Unique Prior ITP is derived as follows: 
◦ 
To derive prior ITP medications, see Section 6.5 
◦ 
To derive unique: count all medications with 
 as one, count all 
medication with 
 as one, for remaining prior ITP medications count all 
unique standardized medication names (CMDECOD) 
6.2.2 
Lifestyle 
A listing for DILI CRFs (DILI patients only) data (alcohol use and illicit drug use in the past six 
months (yes/no)) will be created using the RS. 
6.3 
Previous and ongoing medical history  
Previous and ongoing medical history will be summarized by treatment group and overall system 
organ class (SOC), high level group term (HGLT), high level term (HLT) and preferred term 
(PT). Medical procedures are not coded.  
Previous and ongoing medical history will be listed (separated) for the RS by treatment group 
and will include the MedDRA SOC, high level group term (HGLT), high level term (HLT) and 
PT.  
6.4 
Procedure history and concomitant medical procedures 
Procedure history and concomitant medical procedures will be listed using the RS. 
6.5 
Concomitant medications  
Definitions:  
Past Medications: defined as any medications that started and stopped before first 
administration of IMP. 
This includes medications reported in the following eCRF pages: 
- 
“ITP Treatment history”  
- 
“Prior and Concomitant Medications”, if end date before first IMP date 
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- 
“Prior and Concomitant Medications ITP Treatment”, if end date before first IMP 
date. 
Prior Medications: defined as any medications that started before the first administration of 
IMP.  
This includes medications reported in the following eCRF pages: 
- 
“ITP Treatment History”,  
- 
“Prior and Concomitant Medications”, if start date before first IMP date. 
- 
“Prior and Concomitant Medications ITP Treatment”, if start date before first IMP 
date. 
Baseline Medications: defined as any medications that started prior to first administration of 
IMP and stopped after the first administration of IMP (classified as prior and concomitant 
medications). This includes medications reported in the following eCRF pages: 
- 
“Prior and Concomitant Medications”, if start date before first IMP date and end date 
after first IMP date or ongoing 
- 
“Prior and Concomitant Medications ITP Treatment”, if start date before first IMP 
date and end date after first IMP date or ongoing 
Concomitant medications: defined as any medication that has been taken at least once after the 
first administration of IMP. 
This includes medications reported in the following eCRF pages: 
- 
“Prior and Concomitant Medications”, if end date after first IMP date or ongoing  
- 
“Prior and Concomitant Medications ITP Treatment”, if end date after first IMP date 
or ongoing 
Concomitant only medication: defined as any medication that started after first administration 
of IMP 
This includes any medication reported in the following eCRF pages: 
- 
“Prior and Concomitant Medications”, if start date after first IMP date 
- 
“Prior and Concomitant Medications ITP Treatment”, if start date after first IMP date 
Table 6-1 below summarizes concomitant medication classification with details around 
medication start and finish. 
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Table 6-1: 
Concomitant Medications Classification 
Medication Started 
Medication finished 
Classification 
Before 1st Dose IMP     Before 1st Dose IMP     Past Medications 
Before 1st Dose IMP     Any time 
Prior Medications 
Before 1st Dose IMP     After 1st Dose IMP        Baseline Medications (= prior and 
concomitant)  
Any time 
After 1st Dose IMP        Concomitant 
After 1st Dose IMP        After 1st Dose IMP        Concomitant Only Medications 
All the categories mentioned above will be summarized separately for ITP medications; Non-ITP 
medications will be listed only (using the RS) to display the number and percentage of 
participants in each category by treatment group, overall and by Anatomical Therapeutic 
Chemical classification (ATC) class, presenting Anatomical Main Group (ATC Level 1), 
Pharmacological Subgroup (ATC level 3), and preferred term.   
Any medications with missing dates will be handled as described in Section 4.2.2 in order to 
classify them as prior and/or concomitant. 
Listings for ITP medications will be also produced using the RS. 
Notes:  
• WHODD Mar2021 will be used for ATC terms. 
6.5.1 
Assignment of medications to treatment period 
• Treatment Period: The treatment period will include medications taken at least once 
between the first administration of IMP on Day 1, up to the earliest of: 
− Week 25 (for participants who roll over to TP0004) 
− 
 after the last dose of IMP 
− The early withdrawal visit. 
• Safety Follow-Up Period: A medication will be assigned to the Safety Follow Up Period if 
it has been taken at least once from the day after the end of the Treatment Period up until the 
EOS visit. 
6.6 
Prohibited concomitant medications and rescue medication 
6.6.1 
Prohibited concomitant medication 
All prohibited concomitant medication listed in section 6.4.2 in the protocol will be summarized 
on the RS using the number and percentage of study participants who received prohibited 
concomitant medication by ATC class, presenting ATC Level 1, ATC level 3, and PT, ordered 
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alphabetically for the ATC class and in terms of decreasing frequency for PT within ATC class 
by treatment group. In the event of ties, PT will be ordered alphabetically. 
6.6.2 
Rescue Therapy 
All rescue therapies mentioned in section 6.4.3 in the protocol, identified if Rescue Medication is 
ticked as yes on CRF will be summarized using the RS.  
The number and percentage of study participants who received rescue medication will be 
displayed by ATC class, presenting ATC Level 1, ATC level 3, and PT (ordered alphabetically 
for the ATC class and in terms of decreasing frequency for PT within ATC class by treatment 
group. In the event of ties, PT will be ordered alphabetically).  
7 
MEASUREMENTS OF TREATMENT COMPLIANCE 
Not applicable. The number of infusions will be recorded as detailed in Section 10.1. 
8 
EFFICACY ANALYSES 
 All efficacy variables will be listed for all participants by treatment group and visit, and analyses 
performed using the RS unless specified otherwise.   
8.1 
Statistical analysis of the primary efficacy endpoint 
8.1.1 
Primary analysis of the primary efficacy endpoint 
The primary efficacy endpoint will be analyzed according to the following estimands’ attributes: 
(1) Treatment conditions:  Placebo and rozanolixizumab (please refer to section 6 Study 
treatments in the protocol for details) 
(2) Population: Adult Study Participants with Persistent or Chronic Primary Immune 
Thrombocytopenia (ITP) who fulfill the inclusion / exclusion criteria according to the 
protocol. 
(3) Endpoint:  Durable Clinically Meaningful Platelet Response of ≥50x109/L, for at least 8 
out of 12 weeks during the last 12 weeks (Week 13 to Week 25) 
This endpoint includes the platelet count recorded at Week 14 to Week 25 corresponding 
to the response achieved following dosing at Week 13 to Week 24) 
(4) Intercurrent Events: see below. 
 
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Table 8-1: 
Intercurrent Events (ICE), Intercurrent Events Strategies (ICES) and 
Missing data Strategies for the analysis of the primary endpoint 
Intercurrent Events (ICE) 
ICE Strategy 
Missing data strategy 
a) Use of Rescue therapy from 
Baseline prior Week 25 
A composite strategy   
Participants impacted by any 
ICE (a, b, c and d) will be 
considered as non-responders 
after the time of event. 
 
 
Not applicable 
Section 4.2.2 
b) Participants who experience any 
TEAEs leading to permanent 
treatment discontinuation 
c) Participants who discontinue 
prior to receiving IMP  
d) Participants who do not have 
any post-treatment assessment 
e) COVID-19* 
 
A composite strategy   
Participants impacted by ICE 
(e) will be considered as non-
responders at the time of event. 
* COVID-19 Impact category: Temporary discontinuation of study drug, Permanent discontinuation of study drug, 
Termination of study participation and Relationship to COVID-19: confirmed, suspected, general or other as 
recorded in the COVID-19 impact eCRF form. 
(5) Population-level summary: Owing to early termination of the study, the population-level 
summary will be provided using descriptive statistics. 
8.2 
Statistical analysis of the secondary efficacy endpoints 
8.2.1 
Cumulative number of weeks with Clinically Meaningful Platelet Response 
of ≥50x109/L over the 24-Week treatment period (Week 1 to Week 25) 
The secondary efficacy endpoint: Cumulative number of weeks with Clinically Meaningful 
Platelet Response of ≥50x109/L over the 24-week treatment period will be analyzed on the RS, 
under the same treatment conditions and population of interest as for the primary endpoint. Note: 
if platelet count was assessed multiple times in a given week, Clinically Meaningful Platelet 
Response only needed to be observed at one timepoint during the week. ICE, ICES and 
population level summary will be handled as described below: 
Table 8-2: 
Intercurrent Events (ICE), Intercurrent Events Strategies (ICES) and 
Missing data Strategies for the analysis of the Cumulative number of weeks 
with Clinically Meaningful Platelet Response of ≥50x109/L over the 24-Week 
treatment period  
Intercurrent Events (ICE) 
ICE Strategy 
Missing data strategy 
a) Use of rescue therapy  
A while on-treatment 
strategy: 
Participants impacted by 
Participants impacted by 
any of the ICE will be 
considered as having a loss 
b) Withdrawal from the study 
due to treatment emergent AE 
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Intercurrent Events (ICE) 
ICE Strategy 
Missing data strategy 
c) Permanent treatment 
discontinuation 
 
any of the ICE will be 
considered as having a loss 
of durable platelet response 
at the time of the ICE 
occurring.   
 
of durable platelet response 
at the time of the ICE 
occurring.  Platelet data up 
to the start date of this ICE 
will be utilized in statistical 
analysis. 
d) COVID-19*  
A composite strategy: data 
impacted by COVID-19 will 
be considered as having a 
loss of durable platelet 
response at the time of the 
ICE occuring. 
Section 4.2.2 
* COVID-19 Impact category: Temporary discontinuation of study drug, Permanent discontinuation of study drug, 
Termination of study participation and Relationship to COVID-19: confirmed, suspected, general or other as 
recorded in the COVID-19 impact eCRF form. 
Population-level summary: Owing to early termination of the study, the population-level 
summary will be provided using descriptive statistics. 
8.2.2 
Time to first Clinically Meaningful Platelet Response of ≥50x109/L: time 
from starting treatment to achievement of first response of ≥50x109/L. 
8.2.2.1 
Definition 
Time to first Clinically Meaningful Response of ≥50x109/L: time from starting treatment to 
achievement of first response of ≥50x109/L (computed as time from starting treatment to 
achievement of first response of ≥50x109/L: Date of first clinically meaningful response - Date 
of first treatment + 1)   
The visit date when the first clinically meaningful response was recorded will be considered as 
the date of first clinically meaningful response. 
8.2.2.2 
Estimand’s attributes  
This secondary efficacy endpoint will be analyzed using the RS, under the same treatment 
conditions and population as for the primary endpoint while using the ICE, ICES described in 
Table 8-3 and the population level summary described below: 
Table 8-3: 
Intercurrent Events (ICE), Intercurrent Events Strategies (ICES) and 
Missing data Strategies for the analysis of Time to first Clinically Meaningful 
Response of ≥50x109/L 
Intercurrent Events (ICE) 
ICE Strategy 
Missing data strategy 
a) Use of rescue therapy prior 
to Week 25 
A while on-treatment 
strategy:  For participants 
impacted by any of the ICE 
(a, b and c).  
Impacted data will be 
excluded from the time at 
risk.  
 
Available platelet data up to 
the start date of this ICE will 
be utilized in statistical 
analysis.  
 
b) Withdrawal from the study 
due to treatment emergent 
AE 
c) Permanent treatment 
discontinuation 
d) COVID-19*  
Composite Strategy: data 
impacted by COVID-19 will 
Section 4.2.2 
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Intercurrent Events (ICE) 
ICE Strategy 
Missing data strategy 
be excluded from the time at 
risk. 
* COVID-19 Impact category: Temporary discontinuation of study drug, Permanent discontinuation of study drug, 
Termination of study participation and Relationship to COVID-19: confirmed, suspected, general or other as 
recorded in the COVID-19 impact eCRF form. 
Population-level summary: Owing to early termination of the study, the population-level 
summary will be provided using descriptive statistics. Median time to event will be estimated as 
median of observed values and also using the Kaplan-Meier estimate. 
8.2.3 
Clinically Meaningful Platelet Response by Day 8, defined as platelet count 
≥50x109/L 
This secondary efficacy endpoint will be analyzed using the RS, under the same treatment 
conditions and population as for the primary endpoint while using the ICE, ICES described in 
Table 8-4 and the population level summary described below: 
Table 8-4: 
Intercurrent Events (ICE), Intercurrent Events Strategies (ICES) and 
Missing data Strategies for the analysis of Clinically Meaningful Response by 
Day 8 
Intercurrent Events (ICE) 
ICE Strategy 
Missing data strategy 
a) Use of rescue therapy up to 
Day 8 
Composite strategy: 
Participants impacted by 
any of these ICE will be 
considered as non-
responders.    
 
Participants with missing data 
due to any of these ICE will 
be considered as non-
responders. 
 
b) TEAEs leading to permanent 
treatment discontinuation 
c) Discontinue prior to receiving 
IMP 
d) Study participant do not have a 
post-treatment assessment up 
to day 8  
e) COVID-19*  
Composite Strategy: 
Participants impacted by 
ICE (e) will be 
considered as non-
responders at the time of 
event. 
Section 4.2.2 
* COVID-19 Impact category: Temporary discontinuation of study drug, Permanent discontinuation of study drug, 
Termination of study participation and Relationship to COVID-19: confirmed, suspected, general or other as 
recorded in the COVID-19 impact eCRF form. 
Population-level summary: Owing to early termination of the study, the population-level 
summary will be provided using descriptive statistics. 
8.2.4 
Response defined as platelet count ≥30x109/L and at least a 2-fold increase of 
the Baseline count confirmed on at least 2 separate occasions at two adjacent 
nominal visits at least 7 days apart, and absence of bleeding 
Definitions: 
a) Two adjacent nominal visits are defined as on-site visits where ITP bleeding scale 
assessment is performed 
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b) Absence of bleeding indicated by Grade 0 for all domains of the SMOG, or a Skin Grade 
of 0 or 1 by visit 
8.2.4.1 
Estimand’s attributes  
Estimated on the RS. The same considerations mentioned in Section 8.2.3, except the endpoint 
which in this case is considered:  Response defined as platelet count ≥30x109/L and at least a 
2-fold increase of the Baseline count confirmed on at least 2 separate occasions at two adjacent 
nominal visits at least 7 days apart, and absence of bleeding. Endpoint will be descriptively 
summarized.  
8.2.4.2 
Sensitivity analysis 
Sensitivity analysis will no longer be performed. 
8.2.5 
Time to first rescue therapy  
Definitions: 
Time to first rescue therapy (in days) is defined as: Date of first rescue therapy use - Date of first 
treatment + 1.  
Participants who are withdrawn due to TEAEs will be censored at the start date of the TEAE, 
and participants who do not take rescue therapy will be censored at the date of withdrawal/study 
completion.  Where there are several AEs which led to drop out, consider the earliest starting 
AE. 
8.2.5.1 
Estimand’s attributes  
The same considerations for treatment conditions and population of interest as mentioned in 
items 1 and 2 in Section 8.1.1, except the endpoint which is described above and the following 
approach for ICE (see Table 8-5) and the population level summary: 
Table 8-5: 
 Intercurrent Events (ICE), Intercurrent Events Strategies (ICES) and 
Missing data Strategies for the analysis of Time to first rescue therapy 
Intercurrent Events (ICE) 
ICE Strategy 
Missing data strategy 
a) Withdrawal from the study 
due to TEAE 
 
A composite strategy: 
Participants will be 
considered censored at the 
time of the ICE. 
Not applicable 
b) COVID-19*  
A composite strategy: 
 
Section 4.2.2 
* COVID-19 Impact category: Temporary discontinuation of study drug, Permanent 
discontinuation of study drug, Termination of study participation and Relationship to COVID-
19: confirmed, suspected, general or other as recorded in the COVID-19 impact eCRF form. 
Population level summary: Endpoint will be descriptively summarized.  Median time to event 
will be estimated using the Kaplan-Meier estimate.  
8.2.6 
Change from Baseline to Week 25 in ITP-PAQ Symptom score  
Change in ITP-Patient Assessment Questionnaire (ITP-PAQ, see section 8.1.3.1 in the protocol 
for details) Symptom score will be calculated at week 25 relative to the Baseline and will be 
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limited to the participants with a Baseline ITP-PAQ score available. Endpoint will be 
descriptively summarized. Please see Section 13.5 for details about ITP-PAQ scoring and ITP-
PAQ scales. 
8.3 
Statistical analysis of other efficacy endpoints 
8.3.1 
Cumulative number of weeks over the planned 24-Week treatment period 
with platelet counts ≥30×109/L and at least doubling from Baseline. 
Cumulative number of weeks over the planned 24-Week treatment period with platelet counts 
≥30×109/L and at least doubling from Baseline will be summarized descriptively using the RS 
and listed.   
The same considerations for treatment conditions and population of interest as mentioned in 
items 1 and 2 in Section 8.1.1, except the endpoint which is described above and the following 
approach for ICE (see Table 8-6) and the population level summary: 
Table 8-6: 
Intercurrent Events (ICE), Intercurrent Events Strategies (ICES) and 
Missing data Strategies for the analysis of cumulative number of weeks over 
the planned 24-Week treatment period with platelet counts ≥30×109/L and at 
least doubling from Baseline.. 
Intercurrent Events (ICE) 
ICE Strategy 
Missing data strategy 
a) Use of rescue therapy prior to 
Week 25 
Composite strategy: 
Participants impacted 
by any of these ICE of 
interest will be 
considered as non-
responders.    
Participants with missing values 
due to any of these ICE of 
interest will be considered as 
non-responders. 
b) TEAEs leading to permanent 
treatment discontinuation 
c) Discontinue prior to receiving 
IMP 
d) Study participant do not have 
a valid Baseline assessment 
e) COVID-19*  
Composite Strategy: 
Participants impacted 
by ICE (e) will be 
considered as non-
responders at the time 
of event. 
Section 4.2.2 
8.3.2 
Mean change from Baseline in platelet count by visit 
Mean change from Baseline in platelet count will be summarized descriptively using the RS at 
each timepoint.  
8.4 
Statistical analysis of exploratory endpoints 
All exploratory variables will be listed only by treatment group and visit. No inferential 
assessments / testing will be performed.  
8.4.1 
ITP Bleeding Score 
8.4.1.1 
ITP-specific Bleeding Assessment Tool (ITP-BAT) bleeding events and 
severity by visit 
ITP-BAT bleeding events by visit, will be listed using the RS.     
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Table 8-7: 
ITP-specific Bleeding Assessment Tool (ITP-BAT) Domains and categories 
Skin 
Mucosal 
Organ 
- Petechiae 
- Ecchymoses 
- Subcutaneous 
Hematomas 
- Bleeding from Minor 
Wounds 
- Epistaxis 
- Oral cavity [a] 
- Subconjunctival 
Hemorrhage 
- Gastrointestinal Bleeding Not 
Explained by Visible Mucosal Bleeding 
or Lesion 
- Lung Bleeding 
- Hematuria 
- Menorrhagia 
- Intramuscular Hematomas 
- Hemarthrosis 
- Ocular Bleeding 
- Intracranial Bleeding 
- Other Internal Bleedings 
[a] Includes gum bleeding, hemorrhagic bullae or blisters, bleeding after bites to lip & tongue or 
after deciduous teeth loss 
Notes:  
− Presence of bleeding will be indicated by a Mucosae or Organs Grade ≥1, or Skin Grade 
≥2.  
− Bleeding reported by the participant without medical documentation will be graded 1. 
− Within each domain, the same grade is assigned to bleeding manifestations of similar 
clinical impact.  
− The “worst” bleeding manifestation since the last visit will be graded, and the highest 
grade within each domain will be recorded. 
Please see Section 13.6  ITP bleeding score for more details. 
8.4.1.2 
ITP bleeding at Screening 
Data collected in the Bleeding Assessment Tool – Screening eCRF will be listed using the RS. 
8.4.1.3 
Presence/Absence of ITP bleeding  
The number and percentage of participants with absence/presence of bleeding (see definitions 
below) will be summarized, and individual participants will be listed at each visit. 
• Presence of bleeding is indicated by a Grade of 1 or above, for at least one domain of the 
SMOG (except for Skin, where it is Grade 2 or above). 
• Absence of bleeding is indicated by Grade 0 for all domains of the SMOG, or a Skin Grade 
of 0 or 1 
8.4.2 
Effect of Rozanolixizumab on Health-Related Quality of Life (HRQoL) 
8.4.2.1 
European Quality of Life-5 Dimensions, 5 Levels (EQ-5D-5L) item responses 
As described in section 8.1.3.4 in the protocol, the EQ-5D-5L health questionnaire consists of 2 
pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). 
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The descriptive system comprises five dimensions: mobility, self-care, usual activities, 
pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight 
problems, moderate problems, severe problems and extreme problems. The patient is asked to 
indicate his/her health state by ticking the box next to the most appropriate statement in each of 
the five dimensions. This decision results in a 1-digit number that expresses the level selected for 
that dimension. The digits for the five dimensions can be combined into a 5-digit number that 
describes the patient’s health state. 
The EQ VAS records the patient’s self-rated health on a vertical visual analogue scale, where the 
endpoints are labelled ‘The best health you can imagine’ and ‘The worst health you can 
imagine’. The VAS can be used as a quantitative measure of health outcome that reflect the 
patient’s own judgement. 
The EQ-5D-5L essentially consists of 2 pages: the EQ-5D descriptive system and the EQ visual 
analogue scale (EQ VAS). 
Observed values in the European Quality of Life 5 Dimension 5 Levels (EQ 5D 5L) item 
responses and VAS scores will be listed only.  
8.4.2.2 
Short form 36-item (SF-36) domain and composite scores  
The SF-36v2, standard recall, measures the following eight health domains as rated by the 
subjects over the past four weeks: Physical Functioning, Role Physical, Bodily Pain, General 
Health, Vitality, Social Functioning, Role Emotional, and Mental Health. The classification of 
the questionnaire items to the health domains is shown in Section 13.7. 
The SF-36 PCS and MCS scores are used to measure the two broad components, or aspects, of 
health-physical and mental. PCS and MCS are based on the aggregate of the eight health 
concepts described above and all of the eight health domain scales are used to score both 
components summary measures. 
One additional item asks responders about health change over the past year. 
The SF-36 will be used using QualityMetric’s Health Outcomes™ Scoring Software. The 
software uses updated 2009 U.S. population norms and applies a Full Missing Score Estimation 
(Full MSE) method as follows: 
• A health domain score (except the PF domain) will be estimated provided that at least 
one non-missing response is available within that domain 
• For the PF domain item, response theory will be used to develop a model for estimates of 
the missing score 
• Regression methods are then applied to estimate the PCS and the MCS on the basis of the 
available domains. 
 A by-participant listings of SF-36 item responses will be provided. Missing data will not be 
imputed. 
8.4.2.3 
ITP-PAQ Domain Scores 
The ITP-PAQ V1 consists of 44 items that comprise 10 scales. Each of the 10 scales is scored 0 
to 100 according to formula shown in section 13.5, with higher scores indicating better quality of 
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life. Four of the scales measure physical health: Symptoms, Bother, Fatigue, and Activity. Two 
of the scales measure emotional health: Fear and Psychological Health. The remaining four 
scales measure other aspects of QOL: Work QOL, Social QOL, Women’s Reproductive QOL, 
and Overall QOL. 
A by-subject listing of the ITP-PAQ V1 questionnaire, ITP-PAQ V1 item responses will be 
provided by treatment group.  
8.4.3 
Hospitalization due to ITP / Number and length of hospitalizations 
Hospitalizations will be listed. 
8.4.4 
Effect of Rozanolixizumab on Patient Reported Outcomes (PRO) 
8.4.4.1 
FATIGUE-PRO physical fatigue score  
The Fatigue Patient Reported Outcome (PRO) physical fatigue scale consists of 9 items. The 
scale is 1 out of the 3 scales composing the broader Fatigue instrument developed by UCB. Items 
are rated within a 7-day recall period on a 5-point Likert frequency scale ranging from “none of 
the time” to “all of the time.” 
A by-subject listing of the FATIGUE-PRO items will be provided by treatment group. 
8.4.4.2 
Patient Global Impression of Severity (PGI-S) 
The PGI-S consists of a single-state, self-report measure that rates a study participant's severity 
of specific condition, depicting a study participant's rating of overall symptoms (“none”, “mild”, 
“moderate”, “severe”, or “very severe”).  
A by-subject listing of PGI-S will be provided by treatment group.  
8.4.4.3 
Patient Global Impression of Change (PGI-C) 
The PGI-C is a single-state, self-report measure that reflects a study participant's belief about the 
efficacy of treatment for a specific condition. The PGI-C is a 7-point scale depicting a study 
participant's rating of overall improvement (“very much improved,” “much improved,” 
“minimally improved,” “no change,” “minimally worse,” “much worse,” or “very much worse”), 
was planned to be summarized at all available post-baseline visits using descriptive statistics by 
treatment groupon the RS.  
A by-subject listing of PGI-C will be provided by treatment group.  
The PGI-C sample questionnaire is available in the protocol, Appendix 18, Section 10.18. 
9 
PHARMACOKINETICS (PK) AND PHARMACODYNAMICS 
(PD) 
9.1 
Pharmacokinetics  
Individual plasma concentration of rozanolixizumab will be summarized by scheduled sampling 
day for the PK-PPS using n, arithmetic mean, median, SD, minimum, maximum, geometric 
mean (geomean), geometric coefficient of variation (geoCV) and 95% CI (assuming log-
normally distributed data) up to week 4. 
The following rules will apply for PK data listings and summaries: 
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• Values below the LLOQ will be reported as below the limit of quantification (BLQ) 
• Descriptive statistics of concentrations will be calculated if at most 1/3 of the individual data 
points at a timepoint are missing or are not quantifiable (<LLOQ). Values that are BLQ will 
be replaced by the numerical value of the LLOQ/2 in this instance.  
• The 95% CI lower and 95% CI upper should be left blank if the SD (or equivalently, the 
geoCV) is 0 
• The geoCV will be calculated using the following formula where SD is the standard 
deviation from the log-transformed data 
geoCV (%) = sqrt[(exp (SD^2) – 1)] x 100 
Individual concentrations of rozanolixizumab will be listed for the RS for each individual with 
the actual time and will include the equivalent dose and actual dose being administered previous 
to the pk sample, the sampling time in days relative to the previous dose, the IgG observed at the 
same visit, the ADA titer observed for the binding assay and the NAb titer for the same visit and 
platelet count for the corresponding visit.   
9.2 
Antidrug antibodies (ADA) 
The immunogenicity analysis should be done on the safety set SS. Samples from study 
participants on placebo will not be tested for anti-drug antibodies. 
Anti-rozanolixizumab antibodies will be measured using a three-tiered assay approach: screening 
assay, confirmatory assay and titration assay. Samples will first be evaluated in the screening 
assay (reported as ‘negative screen’ or ‘positive screen’), followed by analysis of screened 
positive samples in the confirmatory assay to confirm the true positivity of the samples (reported 
as ‘negative immuno-depletion’ or ‘positive immuno-depletion’). Samples that are confirmed as 
positive in the confirmatory assay will be evaluated in a titration assay to quantify the ADA level 
and will be reported as titer (reciprocal dilution factor including minimum required dilution 
(MRD)). Any sample confirmed positive for ADA within the confirmatory assay will be further 
evaluated for the presence of neutralizing anti-rozanolixizumab antibodies.  
Screening, confirmatory, and titer cut points of the respective assays will be determined by the 
bioanalytical laboratory. The relevant statistical reports will be provided as part of the 
bioanalytical reports. Rozanolixizumab has the potential to interfere with the antibody assay at 
concentrations above the drug tolerance limit (DTL); therefore, an integrated evaluation of anti-
rozanolixizumab antibody results and rozanolixizumab plasma concentration will be used to 
enable the interpretation of immunogenicity results.The ADA sample status will be determined 
for each visit where samples were taken for ADA analysis:  
• Sample values that are either ‘negative screen’ or the combination of ‘positive screen’ 
and ‘negative immunodepletion’, will be defined as ADA negative if corresponding 
rozanolixizumab concentrations are equal or below the validated drug tolerance limit of 
the ADA assay (
 rozanolixizumab) allowing detection of 100ng/mL ADA 
• Sample values that are either ‘negative screen’ or the combination of ‘positive screen’ 
and ‘negative immuno-depletion’, but with corresponding rozanolixizumab 
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concentrations above the validated drug tolerance limit of the ADA assay, will be defined 
as ADA inconclusive  
• Sample values that are ‘positive screen’ and ‘positive immunodepletion’ will be defined 
as ADA positive 
• Samples that could not be tested for ADA status due to inadequate sample volume, 
mishandling, or errors in sample collection, processing, storage, etc., will be defined as 
Missing  
• Neutralizing antibody (NAb) sample status (positive/negative/missing) will be 
determined for ADA positive samples. Samples that are NAb positive will be evaluated 
in a titration assay to quantify the NAb level and will be reported as titer. 
The ADA participant status will be classified on individual and group level as outlined below 
(Shankar et al. 2014; Rup et al, 2015). A description of how study participants will be 
categorized for the immunogenicity assessment is provided in Table 9-1.  
Individual study participants will be assessed for ADA participant status, composed of 6 
categories: ADA negative, inconclusive, and ADA positive, whereby a positive participant’s 
status is determined as originating from a treatment-induced, boosted, reduced or unaffected 
ADA response. 
Study participants who are identified as being treatment-induced or treatment-boosted ADA-
positive will be grouped as treatment emergent (TE)-ADA positive participants. Study 
participants who are identified as being treatment-reduced or treatment-unaffected ADA-positive 
will be grouped as non-TE-ADA positive participants. Both TE-ADA positive and non-TE–ADA 
positive participants will be further classified as NAb negative or NAb positive. 
The individual and combined ADA participant categories will be summarized overall through the 
SFU sample if applicable (timepoint of interest). The ADA categories are defined in Table 9-1 
below. 
Notes: 
− The ADA sample status should be determined for each visit where samples were taken 
for ADA analysis. 
ADA Baseline 
By default, the Day 1 will be the Baseline value if the ADA status at screening is ADA negative 
or missing. If the ADA status at screening is ADA positive and ADA status at Day 1 is ADA 
negative or missing, the screening will be the Baseline value. If the ADA status at screening and 
Day 1 are same, Day 1 will be the Baseline value.   
 
 
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Table 9-1: 
Terms and Definitions for ADA Status Evaluation in Study Participants 
Term 
Definition 
Category 
Individual participant categories 
Pre-ADA negative – treatment induced 
ADA negative (ADA-NEG) 
Study participants who have an ADA negative sample 
at Baseline and at all sampling points post-Baseline up 
to the timepoint of interest.  
1 
Inconclusive 
Study participants who have an ADA positive or 
negative Baseline sample and some post-Baseline 
samples are missing or inconclusive, while other post-
Baseline samples are ADA negative up to the 
timepoint of interest.  
2 
Pre-ADA negative – treatment induced 
ADA positive (TI-POS) 
Study participants who have an ADA negative sample 
at Baseline and at least one ADA positive sample at 
any sampling point post-Baseline up to the timepoint 
of interest  
3 
Pre-ADA positive – treatment boosted 
ADA positive (TB-POS) 
Study participants who have an ADA positive sample 
at Baseline and at least one ADA positive sample at 
any sampling point post-Baseline up to the timepoint 
of interest, with increased titer values compared to 
Baseline (greater than a predefined fold difference 
increase from Baseline value which will be defined 
within the validation of the assay ie MSR of the 
assay1)  
4 
Pre-ADA positive – treatment reduced 
ADA positive (TR-POS) 
Study participants with an ADA positive sample at 
Baseline, and ADA negative samples at all sampling 
points post-Baseline up to the timepoint of interest  
5 
Pre-ADA positive – treatment unaffected 
ADA positive (TU-POS) 
Study participants with an ADA positive sample at 
Baseline and an ADA positive sample at any sampling 
point post-Baseline up to the timepoint of interest, 
with titer values of the same magnitude as Baseline 
(less than a predefined fold difference from the 
Baseline value which will be defined within the 
validation of the assay, ie MSR of the assay1) 
6 
Combined participant categories 
Treatment emergent ADA positive (TE-
POS) 
Includes study participants who are treatment induced 
ADA positive (category 3) or treatment boosted ADA 
positive (category 4). 
7 
Non-treatment emergent ADA positive 
(Non-TE-POS) 
Includes study participants who are treatment reduced 
ADA positive (category 5) or treatment unaffected 
ADA positive (category 6). 
8 
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Table 9-1: 
Terms and Definitions for ADA Status Evaluation in Study Participants 
Term 
Definition 
Category 
Treatment emergent ADA positive – 
NAb positive (TE-POS, NAb-POS) 
Includes study participants who are treatment 
emergent positive (category 7) and have at least one 
NAb positive sample 
9 
Treatment emergent ADA positive – 
NAb negative (TE-POS, NAb-NEG) 
Includes study participants who are treatment 
emergent positive (category 7) and have no NAb 
positive samples 
10 
Non-treatment emergent ADA positive - 
NAb positive (Non-TE-POS, NAb-POS) 
Includes study participants who are non-treatment 
emergent positive (category 8) and have at least one 
NAb positive sample 
11 
Non-treatment emergent ADA positive - 
NAb negative (Non-TE-POS, NAb-
NEG) 
Includes study participants who are non-treatment 
emergent positive (category 8) and have no NAb 
positive samples 
12 
1 The fold difference increase from baseline value, ie the minimum significant ratio (MSR) determined during assay 
validation, will be reported in the relevant tables, listings and figures. It reflects the fold difference in titer level that 
considered higher than the assay variation in titer determination. 
The following outputs will be created: 
Summaries on the SS: 
Tables: 
• Number and percentage of participants in the RLZ arm with positive, negative, inconclusive 
or missing sample ADA status at the time of each visit will be summarized overall. 
Denominator is the number of study participants having a non-missing result at that visit.  
• Number and percentage of participants in the RLZ arm in each of the ADA individual 
categories (1 to 6) and combined (7-12) presented above will be summarized overall. 
Denominator will be the total number of study participants having an individual ADA 
participant category defined 
• Summary tables displaying the total prevalence of pre-existing ADA and NAb, and persistent 
ADA positivity in the RLZ arm, as defined below: 
- 
Total prevalence of pre-existing ADA and NAb: number and percentage of participants 
having an ADA positive sample status at baseline, with the denominator being the total 
number of study participants having a non-missing sample result at baseline. The same 
will be repeated for NAb. 
- 
Persistent ADA positivity: Number and percentage of study participants with treatment-
induced ADA positive samples detected at 2 or more sequential sampling time points 
during the treatment (including observation and off-treatment periods), where the first 
and last ADA positive samples are separated by at least 16 weeks (equal to 5 half-lives of 
human IgG [22 days], as per Rup et al., 2015). 
 
 
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Listings: 
Listings by timepoint using the SS will be created. The following datapoints will be included: 
- 
Rozanolixizumab concentration 
- 
Total IgG, and absolute platelet counts  
- 
ADA screening results (with the confirmatory result, the ADA titer result if applicable 
and the ADA sample status)  
- 
NAb result titer (when performed) 
- 
Time since administration of IMP (in days) 
- 
Individual ADA participant classification that apply (as defined above) 
- 
Previous visit actual dose (mg/kg equivalent) and actual dose (mg)  
- 
By-subject listing of immune-Related TEAEs, TEAEs of hypersensitivity reaction, 
anaphylactic reaction, injection site reaction, or autoimmune disorder anti-drug 
antibodies, the time of onset, the ADA and NAb sample status and ADA and NAb titers 
at the closest sampling time point prior to and subsequent to the TEAE, and time since 
last administration of IMP (in days). 
- 
Notes:  Study physician/safety physician/safety lead will mark the Preferred Term of 
immune related AEs based on an excel output of all TEAEs (blinded) after database lock. 
The marked AEs will be used for the summary. 
9.3 
Pharmacodynamic endpoints (PD)  
The following pharmacodynamic endpoints will be based on the SS. 
9.3.1 
Total serum IgG (absolute value) and change from Baseline (absolute value 
and percentage) in serum IgG and in serum IgG subclass concentration at 
each scheduled assessment 
Total serum IgG concentrations will be summarized and listed on the SS by time point for 
absolute values, change from Baseline, and percentage change from Baseline overall and 
stratified by body weight tier.  
IgG subclasses will be listed on the SS by treatment group, and time point for absolute values, 
change from Baseline, and percentage change from Baseline overall  
9.3.2 
Serum immunoglobulin concentrations (IgA, IgE, IgM) at each scheduled 
assessment 
Immunoglobulins (IgE, IgA and IgM) will no longer be summarized; IgE, IgA and IgM 
concentrations will be listed only. 
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9.4 
Influence of Rozanolixizumab on vaccination titers 
9.4.1 
Vaccination titers against Streptococcus pneumoniae, Neisseria meningitidis, 
and Haemophilus influenzae in splenectomized study participants 
Vaccine specific antibodies concentrations will be listed to capture absolute values in vaccination 
titers against Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae in 
splenectomized study participants by visit using the SS. 
9.4.2 
Percent change from Baseline in vaccination titers against tetanus in all 
study participants 
Anti-tetanus toxoid serum titers will be listed to capture absolute values and the percent change 
from baseline in vaccination titers against tetanus in all study participants by visit using the SS. 
10 
SAFETY ANALYSES 
All safety analyses will be presented using the SS. Listings will be presented by period, 
treatment group and participant; tabulations will be presented by period (treatment and safety FU 
Period) and treatment group.  
Unless otherwise specified, safety analyses will be presented by safety treatment group as 
defined in Section 3.6. 
For results disclosure on public registries (eg. ClinicalTrials.gov), treatment-emergent adverse 
events and treatment-emergent serious adverse events will be published. 
10.1 
Extent of exposure 
The following summary will be created using the SS by treatment group: 
a) Study IMP duration and Subject-Years of Time at Risk will be summarized using 
descriptive statistics.  
- 
The number of days on IMP (extent of exposure), will be summarized using 
descriptive statistics for the overall treatment period.   
The number of days on IMP will be calculated as follows:   
Number of days on IMP = [(Date of Last Dose Received) - (Date of First Dose 
Received)] + 1 
 
In all calculations, if a patient dies and the date of death is missing, the date of 
death can be imputed as the date of last infusion of the treatment the participant 
was taking. 
- 
Subject-Years of Time at Risk:  
o For study participants who complete the study as planned and continue 
into an open label study (and, therefore, do not have the SFU visit in the 
parent study) 
Date of last visit – Date of first dose + 1 
o For study participants who die prior to the final visit 
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Date of death – Date of first dose + 1 
o For all other study participants, use the minimum of the following: 
Date of last dose – Date of first dose + 56 
Date of last clinical contact – Date of first dose + 1 
o This last group could include study participants who discontinue early, 
study participants who complete the study as scheduled but choose not to 
continue into an open label study, or study participants who are ongoing in 
the SFU period at the time of the data snapshot. 
- 
The total time at risk is calculated as the sum of the person-time at risk (days) 
across all participants in the population divided by 365.25. 
As described in the protocol, a fixed-unit doses across body weight tiers and treatment arms will 
be employed in this study according to the following scheme, as presented in Table 10-1 below 
Table 10-1: 
TP0003 dose levels and weight tiers of rozanolixizumab 
 
 
Bodyweight 
 
Starting dose 
 
Maintenance dose 
level 1 
 
Maintenance 
dose 
level 2 
 
Maintenance 
dose level 3 
>35 to <50kg 
 
 
 
No weight 
adjustment 
 
≥50 to <70kg 
 
 
 
≥70 to <100kg 
 
 
 
≥100kg 
 
 
 
Note: the starting dose of 
 is not applicable in Protocol Amendment 3, but is applicable 
in earlier protocol versions. 
If a study participant is in the lowest body weight tier (below 50kg) and is on the lowest dose 
level with a platelet count between >150×109/L and <400×109/L, the investigator might decide to 
temporarily stop treatment according to medical judgement based on the observation of platelet 
variability. If the platelet count increases above 400×109/L then treatment must be stopped 
anyway. 
The placebo arm will use 0.9% sodium chloride aqueous solution (physiological saline, 
preservative free) for sc administration, matching the volumes of the rozanolixizumab arm. 
A listing with all drug administration details including date, start and stop time of infusion, 
interruptions, discontinuations, dose, volume delivered, percent of planned dose and reasons for 
any interruptions or discontinuations will be created using the SS.  
10.2 
Adverse events 
10.2.1 
Data considerations 
Adverse events will be recorded from the time of informed consent until study completion. All 
AEs will be coded (Section 3.8). 
In addition, AEs will be classified according to the Common Terminology Criteria for Adverse 
Events (CTCAE) Version 5 or later for severity. For any AEs where it is not possible to provide 
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a CTCAE grading, the events will be assessed using a standard intensity classification (mild, 
moderate and severe). For the purpose of the tabulations all CTCAE severity classifications will 
be mapped to a mild/moderate/severe grade as described below:  
CTCAE Toxicity Grade: Severity  
− Grade 1: Mild 
− Grade 2: Moderate 
− Grade 3, 4, 5: Severe 
− Not gradable 
In summaries including intensity, the categories will be summarized according to the following: 
Grade: Intensity  
− Grade 1: Mild 
− Grade 2: Moderate 
− Grade 3: Severe  
For AEs that were not classified according to the CTCAE Toxicity (Severity) criteria, the 
standard intensity Grade will be applied. In case there are mismatches between Severity and 
Intensity Grade, the worst case (i.e., the most severe grade) will be applied.  
Treatment-emergent AEs are defined as AEs starting after the time of first IMP administration up 
to and including 8 weeks (56 days) after the final dose. 
AEs before first dosing and AEs after 8 (56 days) weeks following the final dose will be 
combined in one category and listed. 
Where dates are missing or partially missing, AEs will be assumed to be treatment-emergent 
unless evidence exists that does not allow the AE to be treatment-emergent. Handling of missing 
dates for classification of AEs as TEAEs is described in Section 4.2.2 . 
The following rules will be used to assign a TEAE to a study period:  
TEAE-Treatment Period: a TEAE will be assigned to the Treatment Period for the tabulations 
if the start date of the event is on or after the date of the first administration of IMP on Day 1, up 
to 7 days following the final dose of IMP.  
TEAE-Safety Follow up Period: a TEAE will be assigned to the Safety Follow up Period for 
the tabulations if the start date of the event is greater than 7 days after the date of the final dose 
of IMP until 8 weeks following the final dose; events starting later than 8 weeks following the 
final dose of IMP are not considered TEAEs. 
In the case of early withdrawal in the Treatment Period, a TEAE will be assigned to the 
Treatment Period based on the last received infusion plus 7 days. Subsequent TEAEs (up to 8 
weeks post-last dose) will be assigned to the Safety Follow up Period. 
A TEAE will be counted as a TEAE related to IMP if the response to the question “Relationship 
to Study Medication” is “Related”.  
AEs will be presented as “number of participants (percentage of participants) [number of 
events]”.  In this style of output, “[number of events]” will include all cases of an AE including 
repeat occurrences in individual participants, while “number of participants” will count each 
participant only once. AE analysis will be summarized by Treatment and follow up periods. 
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10.2.2 
Adverse Event Summaries  
The number and percentage of participants who experience AEs will be summarized by 
treatment group. The following outputs will be created: 
(1) Incidence of TEAEs (defined as the number and percentage of participants with at least 
one TEAE (incidence proportion)) – Overview. The following categories will be included 
by treatment arm:  
- 
Any TEAEs 
- 
AESMs 
- 
AESIs 
- 
Serious TEAEs  
- 
TEAEs leading to Study Discontinuation 
- 
Permanent withdrawal from IMP due to TEAEs 
- 
Drug-related TEAEs 
- 
TEAEs with CTCAE Grade 3 and above [or rated as ‘severe’ for events with no 
CTCAE classification]  
- 
All Deaths (AEs leading to death) 
- 
All Deaths (TEAEs leading to death) 
- 
TEAEs leading to dose modification (defined as TEAEs with an action taken with 
study medication of “dose increased” or “dose decreased”) 
- 
TEAEs resulting in temporary treatment interruption 
 
The following summaries will be created by SOC, HLT and PT 
 
(2) 
Incidence of fatal TEAEs by relationship  
(3) 
Incidence of Serious TEAEs by Relationship  
(4) 
Incidence of TEAEs leading to permanent discontinuation of IMP  
(5) 
Incidence of Non-Serious TEAEs Above Reporting Threshold of 5% of participants by 
System Organ Class and Preferred Term 
− AESIs are Potential Hy’s Law, defined as ≥3xULN ALT or AST with coexisting 
≥2xULN total bilirubin in the absence of ≥2xULN ALP, with no alternative explanation 
for the biochemical abnormality. 
−  AESMs are severe headache, severe GI disturbance (ie, diarrhea, abdominal pain, 
vomiting), opportunistic infections, arterial and venous thrombotic and thromboembolic 
events. 
− AESMs and AESIs will be identified based on the assessment by the Investigator as 
recorded in the CRF. An AE will be counted as an AESM if there is a ‘yes’ response to 
the question “Is this an event of Special Monitoring?” and not otherwise. An AE will be 
counted as an AESI if there is a ‘yes’ response to the question “Adverse Event of Special 
Interest?” and not otherwise. 
Listing will be presented by treatment group, most recent dose and participant for all 
AEs. This will include the onset date/time and outcome date/time of the event (including 
relative days), the AE duration, days since first dose of IMP, days since most recent dose 
of IMP, most recent dose, pattern of event, severity/intensity, relationship, action taken 
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and outcome. In addition, the listing will flag AEs that led to discontinuation, TEAEs, 
serious adverse events (SAEs), AESMs, and AESIs. 
AEs of Focus: 
AEs of Focus (AEOF) will be defined using Version 3.0 or later of “Adverse Events of 
Focus for the Rozanolixizumab program”. In addition, worsening thrombocytopenia and 
haemorrhagic events will be included as AEOF as described in AEOF Version 1.4. The 
following AEs are defined in the rozanolixizumab program as AEs of focus (please see 
Section 13.1 for more details)  
− Headaches 
− Gastrointestinal Disturbances 
− Hypersensitivity Reactions 
− Anaphylactic Reactions 
− Injection Site Reactions 
− Infusion Reactions 
− Opportunistic Infections 
− Reductions in Albumin and Plasma Proteins 
− Effects on the Kidney 
− Drug Related Hepatic Disorders 
− Thromboembolic Events 
− Hemorrhagic Events 
− Worsening of Thrombocytopenia 
AEOFs will be listed only. 
10.3 
Vital Signs, Physical Findings, and Other Observations Related to 
Safety 
10.3.1 
Vital Signs and Physical Findings 
The following vital signs measurements will be obtained: 
− Pulse rate 
− Systolic and diastolic blood pressure 
− Temperature (oral, tympanic, or axillary) 
A summary of participants who meet each of the Marked Abnormality (MA) Criteria 
(Appendix 13.3) will be summarized by treatment group at each timepoint. 
A by-participant listing of all vital sign measurements and change from Baseline will be 
presented by treatment group and timepoint. The listing will include a flag for values identified 
as MA criteria (Appendix 13.3). 
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Repeated and unscheduled measurements will be handled as described in Section 4.3. 
10.4 
12-lead Electrocardiograms (ECG) 
12-Lead ECG data (measured values and changes from Baseline) will be listed only. The 
following variables will be reported: 
− Heart rate 
− PR interval 
− RR interval 
− QRS duration 
− QT interval 
− QT corrected for heart rate using Bazett’s formula (QTcB = QT/RR1/2) 
− QT corrected for heart rate using Fridericia’s formula (QTcF = QT/RR1/3) 
A summary of participants who meet each of the Market Abnormally (MA) criteria outlined in 
Appendix 13.4 will be summarized by treatment group at each timepoint and overall. 
All calculations of changes from Baseline will be based on the mean of triplicate assessments at 
each timepoint. If there are not 3 available measurements at a given timepoint, the mean will be 
calculated based on the number of measurements for which data are provided.  
Electrocardiogram findings for the individual triplicate measurements will be listed separately. 
Repeated and unscheduled measurements will be handled as described in Section 4.3. 
10.5 
Clinical Safety Laboratory Assessments  
Laboratory data (as specified in Table 10-1 Protocol-required safety laboratory assessments in 
the protocol) and changes from Baseline (if applicable) for numeric variables will be listed by 
treatment group and timepoint. Values outside the reference range for the numeric variables will 
be flagged in the listings. The reference ranges will also be reported in the listings. In addition, 
the listings will include a flag for values identified as Laboratory assessments – MA Criteria 
(Appendix 13.2). 
Measurements BLQ will be imputed with half of the LLOQ for the purpose of calculating 
change from Baseline. Measurements ALQ, if applicable, will be imputed to the upper 
quantification limit. These rules will be applied to all safety laboratory data including clinical 
chemistry and urinalysis. 
Descriptive statistics will be calculated if at most 1/3 of the individual data points at a time point 
are missing or are either not quantifiable (<LLOQ) or ALQ. Values that are BLQ will be 
replaced by the numerical value of the LLOQ/2 in this instance and values that are ALQ will be 
imputed to the value of the upper quantification limit. If more than two-thirds of the individual 
data points at a timepoint are missing or not quantifiable (BLQ and/or ALQ), no descriptive 
statistics will be calculated. 
The following summaries/tables will be created: 
 
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− A summary of participants who meet each of the Laboratory assessments – MA criteria 
(Appendix Section 13.2 ) will be summarized by treatment group at each timepoint. 
A listing for laboratory assessments will be also created using the SS. 
10.5.1 
Potential Drug-Induced Liver Injury 
Data from subjects with any of the laboratory results meeting the criteria for potential drug-
induced liver injury (PDILI) (below) was planned to be summarized by treatment arm and visit 
using the SS to include: 
− Subjects with at least one post-Baseline liver laboratory assessment 
− Incidence of potential hepatotoxicity with symptoms potentially associated with hepatitis 
or hypersensitivity, which will account for the number and percentage of subjects 
meeting laboratory criteria for PDILI for at least 1 visit and reporting at least 1 symptom 
potentially associated with hepatitis or hypersensitivity according to the Investigator on 
the PDILI CRF) 
− Incidence of potential hepatotoxicity with no symptoms potentially associated with 
hepatitis or hypersensitivity, which will account for the number and percentage of 
subjects meeting laboratory criteria for PDILI for at least 1 visit and not reporting any 
symptom potentially related to hepatitis or hypersensitivity according to the Investigator 
on the PDILI CRF 
− Number and percentage of study participants who meet the Laboratory criteria for PDILI 
(see table below) 
Table 10-2: 
Laboratory criteria for PDILI 
Laboratory Criteria 
Comments 
(AST or ALT > 3 x ULN) and TBL > 1.5 x ULN 
- All values must be met at the same sample 
taken from the same visit 
(AST or ALT > 3 x ULN) and TBL > 2 x ULN 
(AST or ALT > 3 x ULN) and TBL > 2 x ULN 
and ALP < 2 x ULN  
- All values must be met at the same visit 
- Subjects who potentially meet Hy’s law 
criteria at least 1 time during exposure. To 
be counted as potential Hy’s Law, all 
criteria must be met at the same sample 
taken at the same visit. 
ALP = Alkaline phosphatase; ALT = Alanine aminotransferase; AST = Aspartate aminotransferase; TBL = total 
bilirubin; ULN = upper limit of normal range. 
A listing will be created only for visits for which at least one of the above criteria was fulfilled 
for a given participant and will display all results obtained at that visit for the specified 
parameters.  The listing will specify AST, ALT, TBL, and ALP. 
10.6 
Concentrations of Total Protein and Albumin  
Concentrations of total protein and albumin for each visit (as described in the schedule of events 
in the protocol) will be listed using the SS. 
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10.7 
Serum and Plasma Complement Levels 
Serum (C3 and C4) and plasma (C3a and C5a) complement variables will be listed by treatment 
group and time point. 
Measurements below the limit of quantification (BLQ) will be imputed with half of the lower 
limit of quantification (LLOQ). Measurements above the limit of quantification (ALQ), if 
applicable, will be imputed to the upper limit of quantification. 
All analyses described in this section will be performed on the SS. 
10.8 
Other Safety Variables 
10.8.1 
Physical examination 
Results of physical examination abnormalities will be listed. 
10.8.2 
Pregnancy testing 
Pregnancy testing will consist of serum testing at the Screening. The pregnancy test will be urine 
at all other visits. 
A by-participant listing of the pregnancy test data will be provided by treatment group. 
10.8.3 
Childbearing potential  
Childbearing potential will be collected at Screening. A by participant listing will be provided 
using the RS. 
10.8.4 
Assessment and management of Tuberculosis 
Results of the interferon-gamma release assay tuberculosis (TB) test will be listed. 
Results of the chest X-ray for TB will be listed. 
Results of TB signs and symptoms questionnaire will be listed. 
11 
OTHER ANALYSES  
11.1 
Specific analyses for Pharmaceuticals and Medical Devices Agency 
(PMDA) 
 Separate summaries will not be presented for Japanese participants. 
11.2 
Headache questionnaire 
The results of the headache questionnaire will be listed for each participant. No summary 
tabulations will be provided for these assessments. 
12 
REFERENCES 
Chow SC, Lin M. Analysis of two-stage adaptive seamless trial design. Pharm Anal Acta. 
2015;6(341):2. 
Hedges, Larry V., and Ingram Olkin. "Statistical methods for meta-analysis." (1985). 
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Kuter DJ, Bussel JB, Lyons RM, Pullarkat V, Gernsheimer TB, Senecal FM, et al. Efficacy of 
romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind 
randomised controlled trial. Lancet. 2008;371(9610):395-403. 
Lehmacher W and Wassmer G. Adaptive Sample Size Calculations in Group Sequential Trials. 
Biometrics. 1999;55:1286-90. 
Levey et al. A New Equation to Estimate Glomerular Filtration Rate. Ann Intern Med. 2009; 
150: 604-612. 
Mantel, N., Fleiss, J.L. (1980). Minimum expected cell size requirements for the Mantel-
Haenszel one-degree-of-freedom chi-square test and a related rapid procedure. American 
Journal of Epidemiology 112, 129-134 
Nehring, S.M.; Goyal, A.; Patel, B.C. (2020). StatPearls Publishing, web link: 
https://www.ncbi.nlm.nih.gov/books/NBK441843/. 
United States Department of Health and Human Services, National Cancer Institute. Common 
Terminology for Adverse Events (CTCAE), Version 5.0, November 17, 2017. 
 
 
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13
APPENDICES
13.1
AE of focus (AEOF) for the Rozimab Program
AEOF Version: 3.0 or later, Date: 13Dec2021 will be used in this SAP as described 
below.  In addition, worsening thrombocytopenia and haemorrhagic events will be included as 
AEOF as described in AEOF Version 1.4:
ARTICLE I. MedDRA 22.0 and 22.1 and 23.0 and 23.1 AND 24.0
The purpose of this document is to detail the approach to identifying TEAEs meeting criteria for 
AEs of focus (AEOF) for the Rozanolixizumab (also called Rozimab) program. 
The document is organized by MedDRA version. At the time of writing this document, 
MedDRA version 22.0 was planned to be used for all indications under investigation (MG, ITP, 
CIDP, HV). As there is no change between 22.0 and 22.1 and 23.0 and 23.1 and 24.0 regarding 
terms used in below selection criteria, all below specified algorithms apply to these Meddra 
versions.  If future studies are planned which use a different (more recent) version of MedDRA, 
this document will be updated.
The MedDRA SMQ files version 22.0, 22.1, 23.0 and 23.1 are attached in the original document.
MedDRA SMQ file 24.0:
SMQ_spreadsheet_
24_0_English.xlsx
Following Events are Adverse Event of focus For Rozanolixizumab for all indications:
No
Event (also included in 
Title of TFL output)
Selection criteria
Purpose
CSR/ 
SSD/ IB
1
Headache
(Note: also included in 
AESM if severe)
TEAE with HLGT=’Headaches’
CSR/ 
SSD/ IB
2
Gastrointestinal
disturbances
(Note: also included in 
AESM if severe)
TEAE with 
HLT=‘Gastrointestinal and abdominal pains 
(excl oral and throat)’ or 
HLT=‘Gastrointestinal signs and symptoms 
NEC’ or  
HLT=‘Nausea and vomiting symptoms’ or
HLT=‘Diarrhoea (excl infective)‘ or
HLT=‘Gastritis (excl infective)’
CSR/ 
SSD/ IB
3
Hypersensitivity reactions 
SMQ=’Hypersensitivity’
CSR/ 
SSD/ IB
4
Anaphylactic reactions
SMQ=‘Anaphylactic reaction’ and
CSR/ 
SSD/ IB
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TEAEs that either emerged on the same day 
as when a study medication injection 
reaction was received, or that emerged one 
day after a study medication injection was 
received, and which fulfill any of the 
following 3 criteria should be included in the 
summary table: 
 
1. If a subject reports any TEAE which 
codes to a PT included in Category A, 
then the event will be flagged as an 
anaphylactic reaction. 
 
2. If a subject reports any TEAE which 
codes to a PT included in Category B 
AND reports any TEAE which codes to a 
PT included in Category C, and both 
TEAEs have the same start date, then 
both events will be flagged as 
anaphylactic reactions.  
 
3. If a subject reports any TEAE which 
codes to a PT included in Category D 
AND reports (either a TEAE which 
codes to a PT included in Category B 
OR a TEAE which codes to a PT 
included in Category C), and both 
TEAEs have the same start date, then 
both events will be flagged as 
anaphylactic reactions. 
 
5 
Injection site reactions 
TEAE with 
HLT=’Injection site reactions’ or 
HLT=’Infusion site reactions’ or 
HLT=’Administration site reactions NEC’ 
CSR/ 
SSD/ IB 
6 
Infusion Reactions 
 
Infusion reaction marked on AE CRF page 
CSR/ 
SSD/ IB 
7 
Infections 
TEAE with SOC =”Infections and 
infestations”  
Note: This was added as a reminder for 
safety that infections are considered as AE of 
focus and require assessment. No 
programming of this topic is required as 
TEAEs can be found in general AE Tables.  
 
8 
Opportunistic infections 
Opportunistic infections (including 
tuberculosis) will be summarized in a stand-
CSR/ 
SSD/ IB 
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(Note: also included in 
AESM)
alone table using UCB-defined search 
criteria. Opportunistic infections are 
identified in two steps using the attached 
spreadsheet
for MedDRA v24.0:
OI_MedDRA24_0.xls
x
Step 1: Refer to column B of the spreadsheet 
which identifies the Preferred Terms (PTs) to 
be classified as opportunistic infections using 
either a single ‘x’ or a double ‘xx’.
•
TEAEs which code to a PT flagged 
with a single ‘x’ need to also be 
serious in order to be considered an 
opportunistic infection. 
•
All TEAEs which code to a PT 
flagged with a double ‘xx’ are 
considered to be an opportunistic 
infection, regardless of seriousness. 
All serious TEAEs in the study database 
which code to a PT flagged with a single ‘x’ 
and all TEAEs in the study database which 
code to a PT flagged with a double ‘xx’ will 
be summarized as an opportunistic infection 
in the stand-alone table. [CQ97NAM= 
’Opportunistic Infection - Automatic’]
Step 2: Refer to column C of the spreadsheet 
which identifies the PTs that need to be 
evaluated on a case-by-case basis by the 
study physician and safety physician in order 
to determine whether it is a true 
opportunistic infection or not. The process 
for physician review is as follows:
1. Study programming team creates a 
spreadsheet which lists all of the 
subjects with a TEAE present in the 
database which codes to a PT 
identified as case-by-case. 
[CQ98NAM= Opportunistic 
Infection - Manual Review 
Candidate] 
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Information from the AE dataset to 
be included in the spreadsheet: 
Subject ID, AE verbatim term, 
System Organ Class (SOC), High 
Level Term (HLT), Lower Level 
Term (LLT), PT, AE start date, AE 
end date, seriousness, severity, 
relationship to study medication, 
action taken. Additionally, a column 
will be included where the study 
physician/safety physician can 
document their decision on the case. 
2. Study physician/safety physician 
(SPs) reviews the cases in the 
spreadsheet separately and reconciles 
final decision, and indicates in the 
additional column which AEs are 
confirmed to be opportunistic 
infections via a single ‘x’. 
3. Study programming team 
incorporates these decisions into the 
AE dataset by merging the SPs  
decisions for individual subjects / 
PTs and flagging both the automatic 
and the confirmed opportunistic 
infections as such in the dataset. 
 [CQ99NAM= ‘Opportunistic 
Infection – Adjudicated’] 
 
The SPs reviews the context of all of a 
subject’s data (AEs and possibly other) and 
concludes individually.   
Indicators of relevant cases may be e.g. 
repetitive occurrences, conjunction of other 
events or findings considered relevant.  
All subjects with a case-by-case PT reported 
that has been confirmed by the SPs to be an 
OI will be summarized as such in the stand-
alone table, along with all of the events 
identified in Step 1 of this process.  
[CQ99NAM= ‘Opportunistic Infection – 
Adjudicated’]  
The timing and frequency of Step 2 should 
be outlined and agreed to by the study team 
at the beginning of the study. It is suggested 
that this process be executed multiple times 
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13.2 
Laboratory assessments – Marked abnormality criteria 
The following criteria will be applied in the determination of marked abnormalities for 
laboratory assessment values. They are based on Version 5 of the Common Terminology Criteria 
for Adverse Events (CTCAE) grade 3 or higher criteria unless otherwise noted. If both high and 
low criteria are shown for a parameter, the criteria should be summarized separately in tabular or 
graphical data summaries.  
13.2.1 
Hematology 
PARAMETER 
UNIT 
(conventional) 
UNIT 
(standard) 
MARKED 
ABNORMALITY 
CRITERIA 
Hemoglobin  
g/dL 
 
g/L 
<8.0 g/dL; <80 g/L  
WBC (Leukocytes)1 
109/L 
109/L  
Low: <2.0 x 109/L  
High:  >30 x 109/L  
Lymphocytes 
Absolute 
109/L 
109/L  
Low:  <0.5 x 109/L  
High: >20 x 109/L 
Neutrophils Absolute  
109/L 
109/L  
 <1.0 x 109/L   
Platelets2 
109/L 
109/L  
<50.0 x 109/L  
1WBC (Leukocytes) markedly abnormal high criterion is not based on Version 5 CTCAE Grade 3 or higher criteria. 
Due to the mechanism of action of RLZ, the safety alert is related to infection risk which would be identified by a 
lower cut-point than the standard which is related to acute leukemias. A markedly abnormal high cut-point >30 x 
109/L is applied to flag leukocytosis (George 2012). 
2For blinded ITP protocols, Platelets will not be assessed for TEMA because this parameter will be blinded and is 
expected to be abnormally low due to the participant population and entry criteria.  
 
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13.2.2 
Chemistry 
PARAMETER 
UNIT 
(conventional) 
UNIT 
(standard) 
MARKED ABNORMALITY 
CRITERIA 
AST (SGOT) 
U/L 
U/L 
>5.0 x ULN  
ALT (SGPT) 
U/L 
U/L 
>5.0 x ULN  
ALP (Alkaline 
Phosphatase) 
U/L 
U/L 
>5.0 x ULN  
GGT (Gamma 
Glutamyl 
Transferase)1 
U/L 
U/L 
>5.0 x ULN  
Bilirubin (Total) 
mg/dL 
umol/L 
>3.0 x ULN if Baseline value is normal; 
>3.0 x Baseline value if Baseline is 
abnormal  
Albumin 
g/dL 
g/L 
<2 g/dL; <20 g/L  
Creatinine 
mg/dL 
umol/L 
>3.0 x ULN 
Estimate 
glomerular filtrate 
rate (eGFR)2 
mL/min/1.73 
m 
mL/min/1.73 
m 
eGFR <29 mL/min/1.73 m 
C reactive protein 
(CRP)3 
mg/L 
mg/L 
>10mg/L 
Corrected 
Calcium4 
mg/dL 
mmol/L 
Low: Corrected serum calcium of <7.0 
mg/dL; <1.75 mmol/L 
High: Corrected serum calcium of >12.5 
mg/dL; >3.1 mmol/L 
Immunoglobulin 
G5  
(g/L) 
(g/L) 
≤1 g/L 
Potassium 
mmol/L 
mmol/L 
Low: <2.5 mmol/L 
High: >6.0 mmol/L 
Sodium 
mmol/L 
mmol/L 
Low: <125 mmol/L  
High: >155 mmol/L 
Glucose6 
mg/dL 
mmol/L 
Low: <40 mg/dL; <2.2 mmol/L  
High: > 250 mg/dL; >13.9 mmol/L 
Total Cholesterol1 
mg/dL 
mmol/L 
>400 mg/dL; >10.34 mmol/L  
Triglycerides1 
mg/dL 
mmol/L 
>500 mg/dL; >5.7 mmol/L 
Abbreviations: ALT= alanine aminotransferase; AST = aspartate aminotransferase; dL = deciliter; GGT: gamma-
glutamyltransferase; L = liter; mg = milligram; mmol = millimoles; μg = microgram; U = unit; ULN = upper limit 
of normal 
Note: Marked abnormality criteria are defined by Grade 3 or higher events according to the CTCAE, Version 5.0  
unless otherwise noted.  
1GGT, Total Cholesterol and Triglycerides were to be collected under Protocol Amendment 3 but were not collected 
under Protocol Amendment 2. Since no participants were enrolled under Protocol Amendment 3, these laboratory 
assessments will not summarized or listed. 
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2eGFR is calculated using the Chronic Kidney Disease Epidemiology Collaboration or CKD-EPI formula 
(https://qxmd.com/calculate/calculator_251/egfr-using-ckd-epi) which is eGFR = 141 * min(Scr/κ,1)α * 
max(Scr/κ, 1)-1 209 * 0.993Age * 1.018 [if female] * 1.159 [if black];  where Scr is serum creatinine (mg/dL), κ is 0.7 
for females and 0.9 for males, α is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/κ or 
1, and max indicates the maximum of Scr/κ or 1. For derivation from values in standard units (umol/L) the κ 
values are 61.9 for females and 79.6 for males. 
3Includes CRP and High Sensitivity (HS) CRP. Reference for marked abnormality criteria: Nehring, S.M.; Goyal, 
A.; Patel, B.C. (2020). StatPearls Publishing, web link: https://www.ncbi.nlm.nih.gov/books/NBK441843/. A 
moderate elevation of CRP level per referred reference is used for the marked abnormality criteria for RLZ to 
ensure a change suggestive of inflammatory process is captured. 
4Corrected Calcium = 0.02 * (40 – albumin (g/L)) + calcium (mmol/L) 
5Immunoglobulin G criterion based on immunodeficiency literature and noted in RLZ study protocols. 
6Glucose high criterion defined by Grade 3 and higher events according to CTCAE, Version 4.03, June 14, 2010. 
 
 
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13.3 
Vital sign assessments - abnormal 
Abnormality criteria to be applied in the assessment of vital signs parameter values are given 
below. 
PARAMETER 
ABNORMALITY CRITERIA 
Pulse Rate (beats/minute) 
 
<50 and a decrease from Baseline of ≥15 
>120 and an increase from Baseline of ≥15 
Systolic Blood Pressure (mmHg) 
≤ 90 and a decrease from Baseline of ≥20 
≥ 180 and an increase from Baseline of ≥20 
Diastolic Blood Pressure (mmHg) 
<50 and a decrease from Baseline of ≥15 
>105 and an increase from Baseline of ≥ 15 
Temperature 
>101 0F (38.3 0C) 
Body Weight 
 ≥ 10% decrease from Baseline 
≥ 10% increase from Baseline 
13.4 
Electrocardiogram (ECG) – Abnormal 
Abnormality criteria to be applied in the assessment of ECG parameter values are given below: 
Parameter 
Abnormality Criteria 
QT interval (ms) 
 
≥500ms 
≥60ms increase from Baseline 
QTc(F) (ms) 
≥500ms 
≥60ms increase from Baseline 
PR interval (ms) 
Treatment-emergent value >200ms 
QRS interval (ms) 
Treatment-emergent value >100ms 
Heart rate (bpm) 
<50bpm 
>120bpm 
Abbreviations: BL= Baseline, bpm = beats per minute; ms = milliseconds; QTc(F) = Fridericia corrected 
QT interval;  
Note: Treatment-emergent is defined as meeting the criteria at any post-Baseline visit during the 
Treatment Period (including unscheduled visits) and not meeting the same criteria during Baseline 
 
 
 
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13.5 
ITP-PAQ Scoring 
13.5.1 ITP-PAQ Scales 
Please see below for the items associated for each scale and the number of points in the 
Likert Scale that will be used per scale where higher numbers mean better health status. 
Question 
Scale 
Response Categories 
1 
Physical Health: symptoms  
0-4 
2 
  
3 
  
4 
  
5 
  
6 
  
7 
Physical Health: fatigue 
0-4 
8 
  
9 
  
10 
  
11 
Physical Health: bother 
0-4 
12 
0-6 
13 
0-6 
14 
Physical Health: activity 
0-4 
15 
0-4 
16 
Emotional Health: psychological 
0-4 
17 
0-4 
18 
0-4 
19 
0-4 
20 
0-4 
21 
Emotional Health: fear 
0-4 
22 
0-4 
23 
0-4 
24 
0-4 
25 
0-4 
26 
Overall QoL 
0-6 
27 
0-6 
28 
0-3 
29 
0-3 
30 
0-3 
31 
Social Activity 
0-4 
32 
0-4 
33 
0-4 
34 
0-4 
35 
Women’s reproductive health 
0-4 
36 
0-4 
37 
0-4 
38 
0-4 
39 
0-4 
40 
0-4 
41 
Work 
0-5 
42 
0-5 
43 
0-5 
44 
0-5 
 
 
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The ITP-PAQ domain scores will be obtained by transforming the raw sum of the item 
responses to a 0-100 scale. This can be obtained using the following formula: 
 
ITP-PAQ score = Sum of  item scores within the scale
raw sum range
∗100 
 
ITP-PAQ domain 
Raw sum range 
Symptoms 
24 
Fatigue 
16 
Bother 
16 
Activity 
8 
Psychological health 
20 
Fear 
20 
Work 
20 
Social activity 
16 
Women’s reproductive health 
24 
Overall Quality of Life 
21 
 
Missing data: 
A domain score is not calculated if there is more than half of the items of this domain are 
missing. 
If 50% or more of the items are available, missing items are imputed using the mean of non-
missing items. For domains that include items with a different number of categories, the imputed 
response for missing items has to be transformed on the range of the response scale of the 
missing item. 
 
 
 
 
 
 
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13.6 
ITP bleeding score 
The ITP-BAT tool version 1.0 consists of the following domains: 
− Skin (S) 
− Visible mucosae (M) 
− Organs (O) 
The domain for skin comprises the following bleeding types: 
− Petechiae 
− Ecchymoses 
− Subcutaneous hematomas 
− Bleeding from minor wounds 
The domain for visible mucosae comprises the following bleeding types: 
− Epistaxis 
− Oral cavity- gum bleeding 
− Oral cavity – hemorrhagic bullae or blisters 
− Oral cavity – bleeding from bites to lips and tongue or after deciduous teeth loss 
− Subconjunctival hemorrhage (not due to conjunctival disease) 
The domain for organs comprises the following bleeding types: 
− Gastrointestinal bleeding not explained by visible mucosal bleeding or lesion 
− Lung bleeding 
− Hematuria 
− Menorrhagia 
− Intramuscular hematomas 
− Hemarthrosis 
− Ocular bleeding 
− Intracranial bleeding 
− Other internal bleeding 
The grading for each bleeding type within each domain is presented in Table 13-1. Each bleeding 
type is graded based on the worst manifestation that occurred during the most recent observation 
period (since the previous visit). The grade for each domain is then taken as the worst (most 
severe) grade across all bleeding types within that domain. 
Missing data will not be imputed. In the case that data for one or more bleeding types are 
missing within a given domain, the grade for that domain will be evaluated based on the 
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available data. In the case that no data are available within a given domain, the score for that 
domain will not be evaluated at the specific visit. 
Table 13-1: 
ITP-BAT scoring  
Type of 
bleeding 
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE 
LAST VISIT2 
 
0 
1 
2 
3 
4 
SKIN 
 
 
 
 
 
Petechiae 
(does not 
include 
steroid–
induced or 
senile 
purpura)  
 No 
 
 Less than 
or equal to 10 
in a patient’s 
palm-sized 
area3 in the 
most affected 
body area4 
 Any 
number if 
reported by 
the patient 
 
 More than 
10 in a 
patient’s palm-
sized area or 
more than 5 in 
at least 2 
patient’s palm-
sized areas 
located in at 
least 2 different 
body areas4, 
one above and 
one below the 
belt (in the 
most affected 
body areas) 4 
 
 More 
than 50, if 
scattered 
both above 
and below 
the belt  
 
 
Ecchymoses  
 None or 
up to 2 in the 
same body 
area4, but 
smaller than 
a patient’s 
palm-sized 
area, if 
a) 
spontaneous 
or b) 
disproportio
nate to 
trauma/const
riction5 
 
 3 or more 
in the same 
body area4, 
but all smaller 
than a 
patient’s 
palm-sized 
area, if 
a) 
spontaneous 
or  
b) 
disproportiona
te to 
trauma/constri
ction5 
 At least 2 
in two 
 From 1 to 5 
larger than a 
patient’s 
palm-sized 
area, if 
a) spontaneous 
or  
b) 
disproportionat
e to 
trauma/constric
tion5 
with or without 
smaller ones 
 
 
 More 
than 5 larger 
than a 
patient’s 
palm-sized 
area, if 
a) 
spontaneous 
or  
b) 
disproportio
nate to 
trauma/ 
constriction5 
 
 
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Type of 
bleeding 
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE 
LAST VISIT2 
 
0 
1 
2 
3 
4 
different body 
areas4, smaller 
than a 
patient’s 
palm-sized 
area, if 
a) 
spontaneous 
or  
b) 
disproportiona
te to 
trauma/constri
ction5 
 Any 
number and 
size if 
reported by 
the patient  
Subcutaneou
s hematomas 
 
 No 
 
 1 smaller 
than a 
patient’s 
palm-sized 
area 
 Any 
number and 
size if 
reported by 
the patient 
 
 2 smaller 
than a patient’s 
palm-sized 
area, 
spontaneous  
 2 smaller 
than a patient’s 
palm-sized 
area, 
disproportionat
e to trauma5 
 
 More 
than 2 
smaller or at 
least 1 
larger than a 
patient’s 
palm-sized 
area, 
spontaneous  
 More 
than 2 
smaller or at 
least 1 
larger than a 
patient’s 
palm-sized 
area, 
disproportio
nate to 
trauma5 
 
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Type of 
bleeding 
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE 
LAST VISIT2 
 
0 
1 
2 
3 
4 
Bleeding 
from minor 
wounds6  
 No 
 
 Lasting 
<=5 min 
 Any 
episode if 
reported by 
the patient  
 
 Lasting >5 
min or 
interfering with 
daily activities  
 
 
Requiring 
protracted 
medical 
observation 
at the time 
of this visit  
 Medical 
report 
describing 
patient’s 
evaluation 
by a 
physician  
 
MUCOSAL 
 
 
 
 
 
Epistaxis7 
 
 No 
 
 Lasting 
<=5 min 
 Any 
episode if 
reported by 
the patient  
 
 Lasting >5 
min or 
interfering with 
daily activities  
 
 Packing 
or 
cauterizatio
n or 
in-hospital 
evaluation 
at the time 
of this visit  
 Medical 
report 
describing 
packing or 
cauterizatio
n or in-
hospital 
evaluation 
 RBC 
transfusion 
or Hb drop 
>2g/dL 
 
 
 
Oral cavity – 
gum 
bleeding7 
 No  
 
 
 Lasting 
<=5 min 
 Any 
episode if 
reported by 
the patient 
 
 Lasting >5 
min or 
interfering with 
daily activities  
 
 
Requiring 
protracted 
medical 
observation 
at the time 
of this visit  
 
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Type of 
bleeding 
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE 
LAST VISIT2 
 
0 
1 
2 
3 
4 
 Medical 
report 
describing 
patient’s 
evaluation 
by a 
physician 
Oral cavity – 
hemorrhagic 
bullae or 
blisters  
 No 
 
 Less than 
3 
 Any 
number if 
reported by 
the patient 
 
 From 3 to 
10 but no 
difficulty with 
mastication  
 
 More 
than 10 or 
more than 5 
if difficulty 
with 
mastication 
 
Oral cavity - 
bleeding 
from bites to 
lips & tongue 
or after 
deciduous 
teeth loss 
 No 
 
 Lasting 
<=5 min 
 Any 
episode if 
reported by 
the patient  
 
 Lasting >5 
min or 
interfering with 
daily activities 
 
 
 
Intervention
s to ensure 
hemostasis 
or in-
hospital 
evaluation 
at the time 
of this visit 
 Medical 
report 
describing 
intervention
s to ensure 
hemostasis 
or in-
hospital 
evaluation 
 
Subconjuncti
val 
hemorrhage  
(not due to 
conjunctival 
disease) 
 No 
 
 Petechiae/ 
hemorrhage 
partially 
involving one 
eye 
 Any 
episode if 
 Petechiae/ 
hemorrhage 
partially 
involving both 
eyes, or diffuse 
hemorrhage in 
one eye  
 Diffuse 
hemorrhage 
in both eyes 
 
 
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Type of 
bleeding 
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE 
LAST VISIT2 
 
0 
1 
2 
3 
4 
reported by 
the patient  
 
 
 
ORGAN (and 
internal 
mucosae) 
 
 
 
 
 
 
Gastrointesti
nal bleeding 
not explained 
by visible 
mucosal 
bleeding or 
lesion: 
Hematemesis, 
Melena, 
Hematochezia
, 
Rectorrhagia 
 No 
 
 Any 
episode if 
reported by 
the patient 
  
 Present at 
the visit  
 Described 
in a medical 
report  
 
 
Requiring 
endoscopy8 
or other 
therapeutic 
procedures 
or in-
hospital 
evaluation 
at the time 
of this visit 
 
 Medical 
report 
prescribing 
endoscopy8 
or other 
therapeutic 
procedures 
or in-
hospital 
evaluation 
 
 RBC 
transfusion 
or Hb drop 
>2g/dL 
 
 
Lung 
bleeding 
Hemoptysis 
Tracheobronc
hial bleeding 
 No 
 
 Any 
episode if 
reported by 
the patient 
 
 Present at 
this visit 
 Described 
in a medical 
report  
 
 
Requiring 
bronchosco
py8 or other 
therapeutic 
procedures 
or in-
hospital 
evaluation 
 RBC 
transfusion 
or Hb drop 
>2g/dL 
 
 
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Type of 
bleeding 
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE 
LAST VISIT2 
 
0 
1 
2 
3 
4 
at the time 
of this visit  
 An 
equivalent 
episode if 
described in 
a medical 
report  
 
Hematuria  
 No 
 
 Any 
episode if 
reported by 
the patient 
 
Microscopic 
(lab analysis 
exhibited) 
 
 
 
Macroscopic 
(lab analysis 
exhibited) 
 
 Described 
in a medical 
report  
 
 
Macroscopi
c, and 
requiring 
cystoscopy8 
or other 
therapeutic 
procedures 
or in-
hospital 
evaluation 
at the time 
of this visit 
 An 
equivalent 
episode if 
described in 
a medical 
report  
 RBC 
transfusion 
or Hb drop 
>2g/dL 
 
Menorrhagia 
(compared to 
pre-ITP or to 
a phase of 
disease with 
normal 
platelet 
count)9 
 
 No 
  
 Doubling 
nr. of pads or 
tampons in 
last cycle 
compared to 
pre-ITP or to 
a phase of 
disease with 
normal 
platelet count 
 Score 
>100 using 
 Changing 
pads more 
frequently than 
every 2 hrs. or 
clot and 
flooding 
 
 Requiring 
combined 
treatment with 
antifibrinolytic
s and hormonal 
 Acute 
menorrhagia 
requiring 
hospital 
admission 
or 
endometrial 
ablation 
(either at 
this visit or 
described in 
 RBC 
transfusion 
or Hb drop 
>2g/dL  
 
 
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Type of 
bleeding 
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE 
LAST VISIT2 
 
0 
1 
2 
3 
4 
PBAC in the 
last cycle, if 
normal score 
in pre-ITP 
cycles or in a 
phase of 
disease with 
normal 
platelet count 
therapy or 
gynecological 
investigation 
(either at this 
visit or 
described in a 
medical report)  
a medical 
report)  
 
  
Intramuscula
r hematomas 
(only if 
diagnosed by 
a physician 
with an 
objective 
method)  
 
 No 
 
 
 Post 
trauma, 
diagnosed at 
this visit, if 
judged 
disproportiona
te to trauma 
 An 
equivalent 
episode if 
described in a 
medical report  
 
 
Spontaneous, 
diagnosed at 
this visit  
 
 An 
equivalent 
episode if 
described in a 
medical report  
 
 
Spontaneou
s or post 
trauma (if 
judged 
disproportio
nate to 
trauma) 
diagnosed at 
this visit 
and 
requiring 
hospital 
admission 
or surgical 
intervention 
 An 
equivalent 
episode if 
described in 
a medical 
report  
 RBC 
transfusion 
or Hb drop 
>2g/dL 
 
 
  
 
Hemarthrosis  
(only if 
diagnosed by 
a physician 
with an 
objective 
method) 
 No  
 
 Post 
trauma, 
diagnosed at 
this visit, 
function 
conserved or 
minimally 
impaired, if 
judged 
 
Spontaneous, 
diagnosed at 
this visit, 
function 
conserved or 
minimally 
impaired 
 
 
Spontaneou
s or post 
trauma (if 
judged 
disproportio
nate to 
trauma), 
diagnosed at 
 
Spontaneou
s or post 
trauma (if 
judged 
disproportio
nate to 
trauma) 
diagnosed 
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Type of 
bleeding 
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE 
LAST VISIT2 
 
0 
1 
2 
3 
4 
disproportiona
te to trauma 
 An 
equivalent 
episode if 
described in a 
medical report 
 An 
equivalent 
episode if 
described in a 
medical report  
 
 
this visit 
and 
requiring 
immobilizat
ion or joint 
aspiration 
 An 
equivalent 
episode if 
described in 
a medical 
report 
at this visit 
and 
requiring 
surgical 
intervention 
 An 
equivalent 
episode if 
described in 
a medical 
report  
Ocular 
bleeding 
(only if 
diagnosed by 
a physician 
with an 
objective 
method) 
 No 
 
 
 
 
 Any post 
trauma vitreous 
or retinal 
hemorrhage 
involving one 
or both eyes 
with or without 
impaired/blurre
d vision present 
at this visit if 
judged 
disproportionat
e to trauma 
 An 
equivalent 
episode if 
described in a 
medical report  
 
Spontaneou
s vitreous or 
retinal 
hemorrhage 
involving 
one or both 
eyes with 
impaired/bl
urred vision 
present at 
this visit 
 An 
equivalent 
episode if 
described in 
a medical 
report  
 
 
Spontaneou
s vitreous or 
retinal 
hemorrhage 
with loss of 
vision in 
one or both 
eyes present 
at this visit 
 An 
equivalent 
episode if 
described in 
a medical 
report  
 
Intracranial 
bleeding10: 
intracerebral, 
intraventricula
r, 
subarachnoida
l, subdural, 
extradural  
 No 
 
 
 
 Any post 
trauma event 
requiring 
hospitalization  
 
 Any 
spontaneous 
event 
requiring 
hospitalizati
on in 
presence of 
an 
underlying 
 Any 
spontaneous 
event 
requiring 
hospitalizati
on without 
an 
underlying 
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Type of 
bleeding 
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE 
LAST VISIT2 
 
0 
1 
2 
3 
4 
(only if 
diagnosed 
with an 
objective 
method at the 
visit or 
described in 
a medical 
report 
provided by 
the patient)  
intracranial 
lesion 
  
intracranial 
lesion 
 
Other 
internal 
bleeding: 
hemoperitone
um 
hemopericardi
um 
hemothorax 
retroperitoneal 
bleeding 
hepatic and 
splenic 
peliosis with 
organ rupture 
retroorbital 
bleeding 
metrorrhagia 
etc. 
(only if 
diagnosed 
with an 
objective 
method at the 
visit or 
described in 
a medical 
report 
 No 
 
 
 
 Any 
event 
requiring 
hospitalizati
on <48 hrs. 
 
 Any 
event 
requiring 
hospitalizati
on >48 hrs. 
or RBC 
transfusion 
or Hb drop 
>2g/dL  
 
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Type of 
bleeding 
GRADES BASED ON THE WORST INCIDENT EPISODE SINCE 
LAST VISIT2 
 
0 
1 
2 
3 
4 
provided by 
the patient)  
Grading is based on physical examination at the time of the visit by the physician or expert nurse or on patient’s 
history supplemented by available medical reports. Bleeding manifestations reported by the patient but not visible at 
the time of data collection are graded 1. Grade 5 is assigned to fatal bleeding. 
To receive a grade >1, all non-overt skin and non-overt mucosal bleeding (petechiae, ecchymoses, subcutaneous 
hematomas, vesicles/bullae subconjunctival bleeding) should be visible at the time of visit for grading by the 
physician or expert nurse taking the history.  
For bleeding from minor wounds and overt-mucosal bleeding (epistaxis, gum, bleeding from bites to lips & tongue 
or after deciduous teeth loss/extraction) and all organ bleeding, a medical record describing the symptom or 
indicating a specific intervention/prescription should be also taken into account for grading.  
Requirement for ITP-specific treatments and anti-fibrinolytics (apart from menorrhagia) was not considered for 
grading, due to their subjective nature and their adoption not only to control actual bleeding but also to reduce the 
“risk” of impendent or future bleeding.  
1 In case of patients examined for the first time, all types of bleeding occurring at the visit and in the 15 days 
preceding the visit should be considered.  
2 Each type of bleeding should be graded based on the worst bleeding manifestation that occurred during each 
observation period or in the 15 days preceding the first visit. 
3 Patient’s own palm size is commonly considered to be proportional to body surface area. Palm = the inner 
surface of the hand stretching between the distal crease of the wrist and the bases of the fingers (fingers surface 
excluded). 
4 Body areas include: face, neck, right and left upper limbs (considered separately), right and left lower limbs 
(considered separately), trunk, abdomen, and recumbent areas (for the ambulatory patient means the area below 
the knees).  
5 Bleedings considered proportionate to trauma/constriction on a clinical ground should not be reported for skin 
domain. 
6 Minor wound means superficial skin cuts (eg, by shaving razor, knife, or scissors). 
7 Epistaxis and gum bleeding are also reported in some normal subjects. Thus, a critical judgment is required in 
grading these manifestations; they should be reported only if judged more severe when compared with pre-ITP 
bleeding, if any. 
8 Any endoscopic investigations should be considered for grading only if performed for therapeutic purpose and 
not solely for diagnostic purpose. 
9 In girls at menarche grade 1 cannot be assigned, lacking comparison with previous cycles. 
10 Intracranial bleeding should always be reported, irrespective of its grade. For example, if a woman had S2 
(subcutaneous hematoma) M2 (epistaxis) O3 (menorrhagia) and an intracranial bleeding grade 2 (post trauma, 
requiring hospitalization), the SMOG index is S2M2O3 (intracranial 2). If the same patient also had intracranial 
bleeding grade 3, the SMOG index is S2M2O3 (intracranial 3). 
 
 
 
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13.7 
Classification of the SF-36v2 questionnaire 
Items 
Scales 
3a. Vigorous activities 
3b. Moderate activities 
3c. Lifting or carrying groceries 
3d. Climbing several flights 
3e. Climbing one flight 
3f. Bending, kneeling 
3g. Walking more than a mile 
3h. Walking several hundred yards 
3i. Walking one hundred yards 
3j. Bathing, dressing 
Physical Functioning 
4a. Cut down time 
4b. Accomplished less 
4c. Limited in the kind of work 
4d. Had difficulty performing the work 
Role-Physical 
7. Pain magnitude 
8. Pain interfere 
Bodily Pain 
1 Global health condition rating 
11a. Sick easier 
11b. As healthy 
11c. Health to get worse 
11d. Health excellent 
General Health 
9a. Full of life 
9e. Energy 
9g. Worn out 
9i. Tired 
Vitality 
6. Social extent 
10. Social time 
Social Functioning 
5a. Cut down time 
5b. Accomplished less 
5c. Not careful 
Role-Emotional 
9b. Nervous 
9c. Down in dumps 
9d. Peaceful 
9f. Blue/sad 
9h. Happy 
Mental Health 
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14 
AMENDMENT(S) TO THE STATISTICAL ANALYSIS PLAN 
(SAP) 
14.1 
 AMENDMENT 3 
Rationale for the amendment 
The primary reason for this SAP amendment is to incorporate the changes from Protocol 
Amendment 3 and the reduced scope of analyses following sponsor’s decision to terminate the 
study early. 
Modifications and changes 
Section # and Name 
Description of Change 
Brief Rationale 
2.1.3 
Removed objective “To evaluate the 
effects of rozanolixizumab on exploratory 
biomarkers” 
Updated to align with 
Protocol Amendment 3 
2.1.3 
Added objective “To assess the effect of 
rozanolixizumab on response to 
vaccination in study participants who 
received COVID-19 vaccine” 
2.2.1.2 
Removed “Including all intermediate 
timepoints” from ITP-PAQ endpoint 
2.2.1.4.1 
Changed text of IgG, IgA, IgE and IgM 
endpoints 
2.2.1.4.1 
Removed ITP-specific autoantibodies 
endpoint 
2.2.1.4.2 
Removed several exploratory endpoints 
2.2.1.4.2 
Added COVID-19 vaccination endpoint 
2.2.2.1 
Removed α-globulin, and β-globulin 
endpoints 
2.2.2.1 
Removed Cytokines endpoint 
2.3 
Starting dose of 
 
 
2.3 
Dosing is QW instead of Q2W 
2.3 
Study size reduced to 60 from a maximum 
of 90 participants 
2.3 
Various other changes to study design that 
do not have a direct impact on analysis 
2.4 
Changed derivation of sample size and 
power calculation table 
To reflect the requirement 
to randomize a fixed 
number of participants on 
weekly sc infusions and 
removal of option to 
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Section # and Name 
Description of Change 
Brief Rationale 
increase sample size based 
on an interim analysis 
3.2.4 
Definition of dosing regimen groups 
(weekly and biweekly) 
Need to define subsets of 
protocol-defined analysis 
sets which will be used for 
analysis 
3.5.4 
Change complete infusion to sufficient 
infusion 
Requested by FDA 
3.5.4 
The FAS will no longer appear in any 
analysis 
Owing to the sponsor’s 
decision to terminate this 
study the set is no longer 
required. 
3.5.5 
The PD-PPS will no longer appear in any 
analysis 
Owing to the sponsor’s 
decision to terminate this 
study the set is no longer 
required. 
3.8 
Updated to MedDRA version 24 dictionary 
New version available 
3.8 
Updated to WHODD, Mar 2021 version  
New version available 
3.9 
Text added to describe analysis omitted 
because of early termination of study.  
Sponsor decision to 
terminate study early. 
4.2.1 
Text referring to sensitivity analysis and 
MI MAR analysis removed. 
Analysis no longer 
required. 
4.2.2 
Changed intercurrent event strategy for 
COVID-19 to composite strategy and 
platelet data set to 0 
Requested by FDA 
4.5.2 and throughout 
Remove all references to interim analysis 
and to Stage 1 and Stage 2 analysis 
Interim analysis removed 
in Protocol Amendment 3 
4.7 
Analysis described in this section removed. 
Analysis is no longer 
required. 
4.8 
Analysis removed 
Analysis is no longer 
required. 
6.5.1 
Modification to assignment of medications 
to treatment period 
Be consistent with the 
definition of treatment 
period 
8.1.2 
Sensitivity and supplemental analysis has 
been removed. 
Owing to the sponsor’s 
decision to terminate this 
study the analysis is no 
longer required.  
 
8.1.3 
 
Analysis has been removed. 
Owing to the sponsor’s 
decision to terminate this 
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Statistical Analysis Plan 
Rozanolixizumab 
TP0003 
 
 
 
 
 
 
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Section # and Name 
Description of Change 
Brief Rationale 
 
8.1.4 
Analysis has been removed. 
study the analysis is no 
longer required. 
8.1.5 
Analysis has been removed. 
 
8.2 
 
All formal statistical analysis has been 
removed  
8.3 
Subsections 8.3.1 – 8.3.5 and 8.3.8 – 8.3.9 
have been removed. Statistical analysis has 
been removed from section 8.3.6. 
8.42 
Text modified to reflect that item responses 
will be listed only, no derived scores will 
be calculated, and no change from baseline 
will be computed. 
8.4.4 
Text added to reflect that item responses 
will be listed only, no derived scores will 
be calculated, and no change from baseline 
will be computed. 
9.2 
Updated the analysis for antidrug 
antibodies 
Owing to the sponsor’s 
decision to terminate this 
study the majority of the 
analysis is no longer 
required. 
9.3.1 – 9.3.4 
Changed text of IgG, IgA, IgE and IgM 
endpoints 
Updated to align with 
Protocol Amendment 3 
9.3.5 
Removed ITP-specific autoantibodies 
endpoint 
9.4 
Removed several exploratory endpoints 
10.1 
Clarified definition for time at risk 
Account for participants 
who roll over to TP0004 
 
10.2 
Clarified definitions of severity and 
intensity for adverse events 
Clarify how severe adverse 
events will be summarized 
10.2.2 
Add AESIs and TEAEs leading to study 
discontinuation to overview 
Categories in overview 
should match categories in 
adverse event tables 
10.2.2 
Removed some adverse event tables 
No longer needed 
10.2.2 
Added AEs of focus: hemorrhagic events, 
worsening thrombocytopenia and effect on 
lipids 
These were added to the 
AE of Focus document 3.0, 
or they were removed from 
the document but were still 
considered relevant for ITP 
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Statistical Analysis Plan 
Rozanolixizumab 
TP0003 
 
 
 
 
 
 
Confidential 
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Section # and Name 
Description of Change 
Brief Rationale 
10.5.1 
Added “All values must be met at the same 
sample taken from the same visit” 
Clarified how PDILI is 
defined 
10.5.1 
Added the components of the Hy’s law 
definition presented separately in a 
stepwise fashion to the table 
Provide more information 
about the components of 
PDILI 
10.6 
Removed α-globulin, and β-globulin 
endpoints 
Updated to align with 
Protocol Amendment 3 
10.7 
Removed change from baseline for 
Complement endpoint 
Owing to the sponsor’s 
decision to terminate this 
study the analysis is no 
longer required. 
10.8 
Removed Cytokines endpoint 
Updated to align with 
Protocol Amendment 3 
13.2.2 
Removed several labs from MA table 
Labs not collected or 
calculated in TP0003 
Throughout 
Minor editorial and formatting changes 
have been made. 
Minor, therefore have not 
been summarized. 
 
 
 
 
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Statistical Analysis Plan 
Rozanolixizumab 
TP0003 
 
 
 
 
 
 
Confidential 
Page 85 of 85 
 
 
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE 
This document has been reviewed and approved per the Review and Approval of Clinical 
Documents Standard Operating Procedures. Signatures indicate that the final version of the 
Statistical Analysis Plan (SAP) or amended SAP is released for execution. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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application and any extensions or variations thereof. 


PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.