Clinical trial NCT05513950
Conditions: Idiopathic Pulmonary Fibrosis
Sponsor: Chiesi Farmaceutici S.p.A.
Start date: 2023-01-25; Completion date: 2024-06-17
Enrollment: 52 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
Assess the safety of CHF10067 (study drug) and any side effects that might be associated with it. The study also evaluated how much of the study drug gets into the bloodstream and how long the body takes to remove it. The body's immune response to the study drug was evaluated.

Chiesi conducted this study in patients affected by idiopathic pulmonary fibrosis (IPF, a progressive and chronic lung disease). Chiesi performed this study to establish the drug doses that would be suitable for future studies (a dose finding study).

Detailed description:
The principal aim of this study was to obtain safety and tolerability data when CHF10067 was administered intravenously as single ascending doses to subjects with IPF (a progressive and chronic lung disease). This information, together with the pharmacokinetic (PK) and immunogenicity data is part of a dose finding efforts, for future clinical studies. The effect of CHF10067 on transglutaminase 2 (TG2) levels was also investigated as an exploratory endpoint.

A sequential group, single ascending dose design has been chosen for safety reasons because CHF10067 is in the early stages of clinical development and no data in the IPF population has been collected so far. In addition, sentinel dosing was used so that in each cohort 2 subjects (1 CHF10067 and 1 placebo) was administered at least 24 hours, before the remaining 6 subjects.

The study was double-blind and placebo-controlled to avoid bias in the collection and evaluation of data during its conduct. Placebo was chosen as the comparison treatment to assess whether any observed effects are treatment-related or reflect the study conditions.

Arms: arm 1: A single intravenous (IV) dose of CHF10067 arm 2: A single dose of placebo (commercial source of 0.9% sodium chloride aqueous solution)
Interventions: intervention 1: CHF10067 starting dose -- 1000mg (Cohort A) intervention 2: CHF10067 intermediate dose -- 2000mg (Cohort B) intervention 3: CHF10067 high dose -- 3000mg (Cohort C) intervention 4: Placebo
Intervention descriptions: intervention 1: Intravenous administration of a starting dose of the monoclonal antibody intervention 2: Intravenous administration of an intermediate dose of the monoclonal antibody intervention 3: Intravenous administration of a high dose of the monoclonal antibody intervention 4: Intravenous administration of a physiological solution as placebo

Protocol documents:
Prot_000.pdf: 
CONFIDENTIAL
Page 1/73
 
CLINICAL STUDY PROTOCOL 
STUDY CODE No.: CLI-10067AA1-01
EUDRACT No.: 2022-001079-15
A PHASE IB, RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED 
STUDY TO INVESTIGATE THE SAFETY, TOLERABILITY, AND 
PHARMACOKINETICS OF AN INTRAVENOUS MONOCLONAL ANTIBODY 
(MAB) AFTER SINGLE ASCENDING DOSES IN SUBJECTS AFFECTED BY 
IDIOPATHIC PULMONARY FIBROSIS
Version No.: 6.0
Date: 06 July 2023
The information contained in this document is confidential and will not be disclosed to others without written 
authorisation from Chiesi Farmaceutici S.p.A., except to the extent necessary to obtain informed consent from 
those persons to whom the drug may be administered or for discussions with local regulatory authorities, Ethics 
Committee/Investigational Review Boards, or people participating in the conduct of the study.
Chiesi Farmaceutici S.p.A.
Via Palermo 26/A
43122 Parma – Italy
NCT05513950




Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 3/73
VERSION HISTORY
Version 
Date 
Change History
1.0
03 May 2022
First version
2.0
25 August 
2022
Protocol version 2.0 (dated 25 August 2022) incorporated the 
following changes into protocol version 1.0 (dated 03 May 
2022) based on Medicines and Healthcare products Regulatory 
Agency (MHRA) feedback:

Section 6.2.2.1 Dose escalation stopping rule was 
updated: ‘Three or more subjects on active drug* 
experience a severe, possibly drug-related AE lasting 
for > 24 hours duration’ is replaced by ‘two or more 
subjects on active drug* experience a severe, possibly 
drug-related AE lasting for > 24 hours duration’. 

Section 10.3 Intensity of Adverse Event was amended 
so that the Common Terminology Criteria for Adverse 
Events (CTCAE) would be used as the adverse event 
severity grading scale rather than a 3-point severity 
grading scale with CTCAE. 

Section 12.3.5.1 Adverse Events was amended to 
change the statistical analysis so that treatment-
emergent adverse event data will be summarised by 
CTCAE grade rather than severe intensity. 
3.0 
24 
October 
2022
See the list of substantial changes in the summary of 
changes dd 24 October 2022.
4.0
22 May 2023
Protocol version 4.0 (dated 22 May 2023) removed the 
bronchoscopy procedure from protocol version 3.0 (dated 
24 October 2022) based on MHRA feedback in the following 
sections:

Section 1.3 Risk/Benefit Assessment

Section 4.1 Subject Recruitment

Section 7.1 Study Schedule – All Cohorts

Section 7.1.2 Optional Additional Visit for 
Bronchoscopy


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 4/73

Section 7.2.12 Optional Bronchoscopy for 
Bronchoalveolar Lavage and Bronchoabsorption 
Assessment

Section 25 References
5.0
16 June 2023
See the list of the substantial changes in the Summary of 
Changes dated 16 June 2023.
6.0
06 July 2023
Non substantial changes to correct inconsistencies related to 
the timing of vital signs and oxygen saturation assessments:
Section 7.1 Footnotes for Evaluation Schedule 
Section 7.2.7.3 Oxygen Saturation
Section 7.2.8 Vital Signs.


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 5/73
PROTOCOL OUTLINE
Study title
A Phase Ib, randomised, double-blind, placebo-controlled study to 
investigate the safety, tolerability, and pharmacokinetics of an intravenous 
monoclonal antibody (mAb) after single ascending doses in subjects affected 
by idiopathic pulmonary fibrosis
Sponsor
Chiesi Farmaceutici S.p.A. - Via Palermo 26/A 43122 Parma - Italy 
Name of the product
CHF10067
Centre(s)
Multi-centre study (approximately 12 sites) 
Indication 
Idiopathic pulmonary fibrosis (IPF)
Study design
Randomised, double-blind, placebo-controlled, single-dose escalation 
Study phase
Phase Ib
Objectives
The primary objective is to assess the safety and tolerability of single 
ascending doses of CHF10067 in subjects with IPF.
The secondary objectives are:

to evaluate the CHF10067 pharmacokinetic (PK) profile in serum 

to evaluate the CHF10067 immunogenicity profile in terms of 
anti-drug antibody (ADA) and neutralising antibody (nAb). 
The exploratory objective is to evaluate transglutaminase 2 (TG2) levels in 
plasma.
Treatment duration
One single dose (CHF10067 or placebo)
Test product 
dose/route/regimen 
A single 1000 mg, anticipated 2000 mg, or anticipated 3000 mg intravenous 
(IV) dose of CHF10067
Reference product 
dose/route/regimen 
A single dose of placebo 
 
Number of subjects
Twenty-four subjects will be studied in 3 cohorts (Cohort A [1000 mg], B 
[anticipated 2000 mg], and C [anticipated 3000 mg]) consisting of 8 subjects 
per cohort. In each cohort, 6 subjects will receive CHF10067, and 2 subjects 
will receive placebo. In each cohort, a minimum of 2 subjects are required 
to be not receiving antifibrotic treatment (including subjects with previous 
use of antifibrotic treatment that has been stopped for at least 2 weeks prior 
to screening).
Study population
Subjects with IPF (not receiving antifibrotic treatment [including subjects 
with previous use of antifibrotic treatment that has been stopped for at least 
2 weeks prior to screening] or receiving standard of care treatments at a 
stable dose for at least 8 weeks prior to screening [nintedanib or 
pirfenidone].
Inclusion/exclusion criteria
Inclusion criteria: 
Subjects must meet all the following inclusion criteria to be eligible for 
enrolment into the study: 


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 6/73
1.
Subject’s written informed consent obtained prior to any 
study-related procedure.
2.
Males or females, of any race, aged ≥ 40 years of age.
3.
Body mass index between 18.0 and 35.0 kg/m2, inclusive.
4.
Body weight ≥ 45 kg.
5.
Diagnosis of IPF as defined by current American Thoracic 
Society/European 
Respiratory 
Society/Japanese 
Respiratory 
Society/Latin American Thoracic Association guidelines (2022), 
which will include subjects with a usual interstitial pneumonia 
(UIP) pattern or probable UIP pattern with confirmation of IPF 
diagnosis based on the Multi-Disciplinary Team Discussion 
(excluding other possible etiological causes of the high-resolution 
computed tomography [HRCT] pattern). Where a lung biopsy is 
available, the computed tomography (CT) pattern and biopsy 
results must be compatible with a diagnosis of IPF. The diagnosis 
of IPF must be within the past 5 years prior to enrolment, and in the 
opinion of the Investigator, has been stable for at least 3 months.[1]
6.
Subjects not receiving any IPF treatment (including subjects with 
previous use of antifibrotic treatment that has been stopped for at 
least 2 weeks prior to screening) or receiving well-tolerated 
standard of care approved treatments at a stable dose for at least 8 
weeks prior to screening (nintedanib or pirfenidone) and it is 
anticipated the dose will remain unchanged throughout the study.
7.
Oxygen saturation ≥ 92% at rest by pulse oximetry while breathing 
ambient air at screening and prior to randomization.
8.
Forced vital capacity (FVC) ≥ 50% of predicted and ratio of forced 
expiratory volume in the first second (FEV1)/FVC ≥ 0.7 at 
screening.
9.
Diffusing capacity of the lung for carbon monoxide (DLCO; 
corrected for haemoglobin) ≥ 35% at screening.
10. Able to understand the study procedures and the risks involved.
11. Female subjects: 
a.
Women of childbearing potential (WOCBP) fulfilling 1 of 
the following criteria: 
i.
WOCBP with fertile male partners: they and/or 
their partner must be willing to use a highly 
effective birth control method preferably with low 
user dependency from the signature of the 
informed consent and until the last study visit or
ii.
WOCBP 
with 
non-fertile 
male 
partners: 
contraception is not required in this case. 
Or
b.
Female subjects of non-childbearing potential defined as 
physiologically incapable of becoming pregnant (i.e., 
post-menopausal or permanently sterile). Tubal ligation or 
partial surgical interventions are not acceptable. If 


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 7/73
indicated, as per Investigator’s request, post-menopausal 
status may be confirmed by screening serum follicle-
stimulating hormone levels (according to local laboratory 
ranges). 
12.  Males fulfilling one of the following criteria: 
a.
Males with pregnant or non-pregnant WOCBP partners: 
they must be willing to use male condom from the 
signature of the informed consent and until the last study 
visit or 
b.
Non-fertile male subjects: contraception is not required in 
this case or
c.
Males with partner not of childbearing potential: 
contraception is not required in this case.
For the definition of WOCBP, fertile men, and the list of highly effective 
birth control methods with low user dependency see APPENDIX 3 or Section 
4.1 of the Clinical Trial Facilitation Group guidance.[16] 
The following inclusion criteria should be re-checked at the Day 1 visit (prior 
to randomisation): 7.
Exclusion criteria: 
The presence of any of the following will exclude a subject from study 
enrolment: 
1.
History of lower respiratory tract infection within 4 weeks prior to 
screening and up to Day 1 of the study, which required the use of 
antibiotics and admission to a clinical facility, or community treated 
lower respiratory tract infection that in the opinion of the 
investigator would preclude the subject’s participation in the study.
2.
History of acute exacerbation of IPF within 3 months prior to 
screening and up to Day 1 of the study, defined as:
a.
worsening or newly developed dyspnoea as reported by the 
subject (≤ 30 days)
b.
new 
bilateral 
ground-glass 
opacities 
on 
HRCT 
superimposed on the UIP abnormalities that defined 
subject eligibility for the study, and
c.
worsening 
hypoxemia 
(in 
the 
judgment 
of 
the 
Investigator), in the absence of pulmonary infection, heart 
failure, or other identifiable causes for this finding.
3.
Planned surgery during the study.
4.
Active diagnosis of lung cancer or a history of lung cancer.
5.
Active cancer or a history of cancer (other than lung cancer) with 
less than 5 years disease free survival time (whether or not there is 
evidence of local recurrence or metastases). Localised carcinoma 
(e.g., basal cell carcinoma or in situ carcinoma of the cervix 
adequately treated, etc.) is acceptable. 


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 8/73
6.
Infiltrative lung disease other than IPF, including any of the 
following:
a.
Other types of idiopathic interstitial pneumonia
b.
Interstitial lung diseases related to exposure to fibrogenic 
agents, other environmental toxins, or drugs
c.
Other types of occupational lung diseases
d.
Granulomatous lung diseases
e.
Pulmonary vascular diseases
f.
Related to systemic diseases (including vasculitis and 
connective tissue diseases).
7.
History of other types of respiratory diseases in the opinion of the 
Investigator, would impact the endpoints in the protocol or 
otherwise preclude the subject’s participation in the study including 
diseases or disorders of the airways, lung parenchyma, pleural 
space, mediastinum, diaphragm, or chest wall.
8.
End-stage fibrotic disease expected to require organ transplantation 
within 6 months.
9.
Trauma or surgical procedures requiring hospitalisation within 
4 weeks prior to screening visit.
10. Subjects exhibiting unhealed wounds or foot ulcers or have known 
history of wound healing complications. 
11. Clinically 
relevant 
and 
uncontrolled 
cardiac, 
hepatic, 
gastrointestinal, renal, endocrine, metabolic, neurologic, or 
psychiatric disorders that may interfere with successful completion 
of this protocol according to the Investigator's judgment.
12. Any abnormal and clinically significant 12-lead electrocardiogram 
(ECG) that in the Investigator's opinion would affect safety 
evaluation or place the subjects at risk at screening and prior to 
randomization. 
13. Chronic heart failure categorized as New York Heart Association 
Class II, III, or IV (this applies to symptoms of chronic heart failure, 
not IPF); clinical diagnosis of cor pulmonale requiring specific 
treatment; or severe pulmonary hypertension requiring specific 
treatment that, in the opinion of the Investigator, would preclude 
the subject’s participation in the study.
14. Currently receiving, or have received, a systemic corticosteroid, 
immunosuppressant, cytotoxic therapy, vasodilator therapy for 
pulmonary hypertension, or unapproved or investigational 
treatment for IPF within 4 weeks prior to screening or prior to 
randomization. Treatment with pirfenidone or nintedanib, though 
not both concurrently, is permitted, provided that the subject has 
been on a well-tolerated stable dose for at least 8 weeks prior to 
screening and it is anticipated the dose will remain unchanged 
throughout the study.
15. Participation in another clinical study with an investigational drug 
in the 1 month or 5 half-lives of that investigational drug 


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 9/73
(whichever is longer) preceding dosing; a longer and more 
appropriate time could be considered by the Investigator based on 
the elimination half-life and/or long-term toxicity of the previous 
investigational drug.
16. Received the coronavirus disease-2019 (COVID-19) vaccine 
≤ 7 days before dosing.  Any systemic symptoms (e.g., myalgia, 
fever, chills, fatigue, etc.) after COVID-19 vaccine should subside 
at least 2 days before the Day 1 visit.
17. Any other drugs which may interfere with the safe completion of 
the study, according to the Investigator opinion, are also forbidden. 
18. Presence of any current infection, or previous infection that 
resolved less than 7 days prior to screening or before treatment 
(with the exception of lower respiratory tract infections, for which 
the exclusion criterion is defined separately: exclusion criterion n. 
1). 
19. Documented COVID-19 diagnosis within the last 4 weeks or which 
has not resolved within 7 days prior to screening or before 
treatment. COVID-19 testing prior to enrolment and during the 
study will be conducted according to current local guidelines and is 
not specified in the protocol.
20. Known intolerance and/or hypersensitivity to any of the excipients 
contained in the formulation or any other substance used in the 
study.
21. History of allergic or anaphylactic reaction to human, humanised, 
chimeric, 
immunoglobulins 
(Igs), 
or 
murine 
monoclonal 
antibodies.
22. History of severe episodes of urticaria and angioedema or diagnosis 
of chronic urticaria and its underlying disorders including, but not 
limited to acquired angioedema due to C1-inhibitor deficiency, 
auto-inflammatory disease, hereditary angioedema, or urticarial 
vasculitis.
23. Confirmed or suspected diagnosis of mastocytosis.
24. Clinically relevant abnormal laboratory values (clinical chemistry 
and haematology) at screening suggesting an unknown disease and 
requiring further clinical investigation or which may impact the 
safety of the subject or the evaluation of the study results according 
to Investigator judgement. Note: in case of abnormal laboratory 
values, that could indicate a temporary condition, the test can be 
repeated twice before randomisation.
25. Positive human immunodeficiency virus (HIV) 1 and/or HIV2 
results at screening.
26. Positive hepatitis result that indicates acute or chronic hepatitis B 
(HB) or hepatitis C (HC) at screening (i.e., positive HB surface 
antigen, HB core antibody [IgM anti-HB core antibody], or HC 
antibody).


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 10/73
27. Blood donation or blood loss (equal or more than 450 mL) within 
2 months prior to screening or prior to randomization.
28. History of cigarette (or e-cigarette) smoking or use of nicotine- or 
tobacco-containing products within 3 months prior to screening or 
a positive urine test for cotinine at screening. 
29. Documented history of alcohol abuse within 12 months prior to 
screening or a positive alcohol breath test prior to randomization. 
Note: before randomization, the test can be repeated once, at least 
3 days after the last positive test, if the Investigator evaluates that 
the subject will be compliant to alcohol abstinence during the study.
30. Documented history of drug abuse within 12 months prior to 
screening or a positive urine drug screen prior to randomization. 
Note: before randomization, the test can be repeated once at least 
15 days after the last positive test, if the Investigator evaluates that 
the subject will be compliant to drug abstinence during the study.
31. Unsuitable veins for repeated venipuncture. 
32. Pregnant or lactating women, where pregnancy is defined as the 
state of a female after conception and until termination of the 
gestation, confirmed by a positive serum human chorionic 
gonadotropin laboratory test. A serum pregnancy test will be 
performed at screening and urine pregnancy test will be performed 
prior to randomisation.
The following exclusion criteria should be re-checked at the Day 1 visit 
(prior to randomisation): 1, 2, 12, 14, 18, 19, 27, and 32. 
Study plan
The screening visit will take place between 3 to 28 days prior to 
randomisation and subject eligibility will be assessed according to the 
inclusion/exclusion criteria. 
On Day 1, subjects will attend the clinical site for an ambulatory visit. 
Following confirmation of eligibility, subjects will be randomised to either 
CHF10067 or placebo and will receive a single IV dose of CHF10067 or 
placebo. Subjects will be monitored for safety, tolerability, immunogenicity, 
PK, and TG2 levels for 84 days post-dose and will attend ambulatory visits 
on Days 2, 5, 7, 14, 28, 56, and 84 (end of study). Even if not mandatory, 
overnight stay is always possible for logistical reasons or to accomplish 
site/subject preferences.
In each cohort, subjects will be divided into 2 sub-groups, with each 
sub-group being dosed at least 24 hours apart. The first sub-group will 
comprise 2 subjects (1 CHF10067; 1 placebo). The second sub-group will 
comprise 6 subjects (5 CHF10067; 1 placebo). The decision to dose the 
remaining 6 subjects will be evaluated by at least the Medical Monitor and 
Sponsor Clinical Research Physician based on the safety data provided by 
the Investigator(s) where the first sub-group have been dosed and the 
decision to escalate to the next dose will be made by the Safety Advisory 
Committee. 


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 11/73
Most relevant allowed 
concomitant treatments
Well-tolerated standard of care treatment of IPF (e.g., nintedanib, 
pirfenidone) at stable doses for at least 8 weeks prior to screening and not 
expected to change during the study. Concomitant intake of nintedanib and 
pirfenidone is not allowed.
COVID-19 vaccine at least 7 days before dosing. Note: Any systemic 
symptoms (e.g., myalgia, fever, chills, fatigue, etc.) after COVID-19 
vaccine should subside at least 2 days before the treatment visit.
Hormone replacement therapy, oral, implantable, transdermal, injectable, or 
intravaginal contraceptives. 
Most relevant forbidden 
concomitant treatments
Systemic corticosteroids, immunosuppressants, cytotoxic therapy or 
vasodilator therapy for pulmonary hypertension, or any other unapproved or 
investigational treatment for IPF. 
In case of exacerbations, appropriate medications can be initiated at 
Investigator’s discretion. 
Any other drug which may interfere with the safe completion of the study, 
according to the Investigator's opinion, is also forbidden.
Safety and immunogenicity 
variables

Adverse events (AEs) and adverse drug reactions

Vital signs (systolic and diastolic blood pressure, pulse rate, 
respiratory rate, and body temperature)

Oxygen saturation measured via pulse oximetry

12-lead ECGs (heart rate, PR, QRS, and QT corrected for heart rate 
by Fridericia's formula)

Physical examinations

Clinical laboratory evaluations: clinical chemistry (including fasting 
glucose) and haematology

Spirometry (FEV1, FVC, FEV1 % of predicted normal and lower limit 
of normal value, FVC % of predicted normal and lower limit of 
normal value, and FEV1/FVC ratio)

Diffusing capacity (DLCO [unadjusted], DLCO % predicted, DLCO 
corrected for haemoglobin, DLCO corrected for haemoglobin % 
predicted, carbon monoxide transfer coefficient, and alveolar volume)

ADAs and nAb

Analysis of systemic markers* of immediate hypersensitivity reaction 
pre-dose and post-dose (post-dose only if required): 
-
Markers of cytokine release syndrome (interferon-γ, tumour 
necrosis factor-α, interleukin [IL]-1 β, IL-2, IL-4, IL-6, IL-8, IL-10, 
IL-12 (p70), and IL-13)
-
Mast cell tryptase 
-
Complement markers (C3a, C5a, CH50, and SC5b-9)
-
CHF10067 IgE
*During the study, the markers analysed may be adjusted as required. Any 
adjustment will be with consideration for subject safety and operational 
activities. 


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 12/73
Pharmacokinetic variables

Area under the concentration-time curve (AUC) from 0 to the last 
quantifiable concentration (AUC0-t)

AUC extrapolated to infinity (AUCinf)

Maximum observed concentration (Cmax)

Time to Cmax (tmax)

Concentration at steady state of infusion (Cinf)

Clearance (CL)

Volume of distribution (Vz)

Terminal half-life (t1/2).
Other variables

TG2 level in plasma
Sample size calculation
This study is designed to explore the safety and tolerability of CHF10067 
for the first time in subjects affected by IPF, while exposing a minimum 
number of subjects; therefore, no formal power calculation was performed. 
A sample size of 24 subjects (8 subjects per cohort; 6 treated with 
CHF10067 and 2 with placebo) is deemed adequate to assess safety and 
tolerability of CHF10067. In each cohort, a minimum of 2 subjects are 
required to be not receiving antifibrotic treatment (including subjects with 
previous use of antifibrotic treatment that has been stopped for at least 2 
weeks prior to screening).
Statistical methods
Safety and Immunogenicity
Safety parameters will be listed and summarised with change from baseline 
(where applicable) at each post-dose timepoint using descriptive statistics 
and 95% confidence intervals (CIs; where applicable). Time profile plots 
will also be presented where relevant. 
The number of events and the number and percentage of subjects 
experiencing treatment-emergent AEs will be presented by treatment. 
Pharmacokinetics 
CHF10067 serum AUC0-t, AUCinf, Cmax, tmax, Cinf, CL, Vz, and t1/2 will be 
summarised 
by 
dose 
level 
using 
descriptive 
statistics. 
Serum 
concentration/time curves will be presented in linear/linear and log/linear 
scale. Plots will be presented by dose level, based on arithmetic means, and 
by subject, by showing the individual curves grouped by dose level (1 plot 
for each dose level) and ADA positivity/negativity (using different colours).
Dose proportionality in terms of CHF10067 AUC0-t, AUCinf, and Cmax will 
be evaluated using the power model including the log-transformed PK 
parameters as dependent variables, and the log-transformed CHF10067 dose 
as a covariate. The slope for log-transformed dose will be estimated with its 
90% CI to examine dose proportionality.
Other
At each post-dose timepoint, TG2 levels in plasma will be summarised using 
descriptive statistics by treatment as absolute value and change from 
baseline using descriptive statistics and 95% CIs. Time profile plots and 
boxplots will also be presented.


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 13/73
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS
ADA
anti-drug antibody
ADL
Activities of Daily Living
ADR
adverse drug reaction
AE
adverse event
ALAT
Latin American Thoracic Society
ATS
American Thoracic Society
AUC
area under the concentration-time curve
AUC0-t
area under the concentration-time curve from 0 to the last quantifiable 
concentration
AUCinf
area under the concentration-time curve extrapolated to infinity
BMI
body mass index
CI
confidence interval
Cinf
concentration at steady state of infusion
CL
clearance
Cmax
maximum observed concentration
COVID-19
coronavirus disease-2019
CTCAE
Common Terminology criteria for Adverse Events
CV
coefficient of variation
DLCO
diffusing capacity of the lung for carbon monoxide
EC
Ethics Committee
ECG
electrocardiogram
eCRF
electronic case report form
ERS
European Respiratory Society 
FEV1
forced expiratory volume in the first second
FSH
follicle-stimulating hormone
FVC
forced vital capacity
GCP
Good Clinical Practice
GMP
Good Manufacturing Practice
HB
hepatitis B
HC
hepatitis C
HIV
human immunodeficiency virus
HRCT
high-resolution computed tomography
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Council on Harmonisation
IFN-γ
interferon-γ
Ig
immunoglobulin
IL
interleukin
ILD
interstitial lung disease
IMP
investigational medicinal product
IPF
idiopathic pulmonary fibrosis
IRT
interactive responsive technology
IV
intravenous
JRS
Japanese Respiratory Society
KCO
carbon monoxide transfer coefficient
KO
knockout


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 14/73
mAb
monoclonal antibody
MedDRA
Medical Dictionary for Regulatory Activities
n
number of observed values
nAb
neutralising antibody
PR
PR Interval
PK
pharmacokinetic
QRS 
QRS Interval
QTcF
QT corrected for heart rate by Fridericia’s formula
SAE
serious adverse event
SAP
Statistical Analysis Plan
SC
subcutaneous
SD
standard deviation
SUSAR
Suspected Unexpected Serious Adverse Reaction
t1/2
terminal half-life
TEAE
treatment emergent-adverse events
TG2
transglutaminase 2
tmax
time to maximum observed concentration
TNF-α
tumour necrosis factor-α
UIP
usual interstitial pneumonia
VA
alveolar volume
Vz
volume of distribution
WOCBP
women of childbearing potential


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 15/73
CONTENT
GENERAL INFORMATION ................................................................................................................................2
VERSION HISTORY.............................................................................................................................................3
PROTOCOL OUTLINE ........................................................................................................................................5
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS......................................................................13
CONTENT.............................................................................................................................................................15
1.
INTRODUCTION.......................................................................................................................................17
1.1 BACKGROUND INFORMATION........................................................................................................................17
1.2 STUDY RATIONALE .......................................................................................................................................18
1.3 RISK/BENEFIT ASSESSMENT..........................................................................................................................18
2.
STUDY OBJECTIVES ...............................................................................................................................19
2.1 PRIMARY OBJECTIVE.....................................................................................................................................19
2.2 SECONDARY OBJECTIVES..............................................................................................................................19
2.3 EXPLORATORY OBJECTIVE............................................................................................................................19
3.
STUDY DESIGN .........................................................................................................................................19
4.
SUBJECT SELECTION CRITERIA........................................................................................................20
4.1 SUBJECT RECRUITMENT ................................................................................................................................20
4.2 INCLUSION CRITERIA.....................................................................................................................................20
4.3 EXCLUSION CRITERIA ...................................................................................................................................22
4.4 SUBJECT WITHDRAWALS ..............................................................................................................................25
5.
CONCOMITANT MEDICATIONS..........................................................................................................26
5.1 PERMITTED CONCOMITANT MEDICATIONS ...................................................................................................26
5.2 NON-PERMITTED CONCOMITANT MEDICATIONS...........................................................................................26
6.
TREATMENT(S) ........................................................................................................................................26
6.1 APPEARANCE AND CONTENT.........................................................................................................................27
6.2 DOSAGE, PREPARATION, AND ADMINISTRATION ..........................................................................................27
6.3 PACKAGING...................................................................................................................................................30
6.4 LABELLING....................................................................................................................................................31
6.5 TREATMENT ALLOCATION ............................................................................................................................31
6.6 TREATMENT CODE ........................................................................................................................................31
6.7 TREATMENT COMPLIANCE ............................................................................................................................32
6.8 DRUG STORAGE.............................................................................................................................................32
6.9 DRUG ACCOUNTABILITY...............................................................................................................................33
6.10 PROVISION OF ADDITIONAL CARE...............................................................................................................33
7.
STUDY PLAN..............................................................................................................................................34
7.1 STUDY SCHEDULE – ALL COHORTS ..............................................................................................................34
7.2 INVESTIGATIONS ...........................................................................................................................................39
8.
PHARMACOKINETIC AND OTHER ASSESSMENTS.......................................................................48
8.1 PHARMACOKINETIC ASSESSMENTS ...............................................................................................................48
8.2 OTHER ASSESSMENTS ...................................................................................................................................49
9.
SAFETY ASSESSMENTS..........................................................................................................................49


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 16/73
9.1 SAFETY VARIABLES ......................................................................................................................................49
9.2 EMERGENCY SITUATION ...............................................................................................................................50
10.
ADVERSE EVENT REPORTING............................................................................................................51
10.1 DEFINITIONS................................................................................................................................................51
10.2 EXPECTEDNESS ...........................................................................................................................................52
10.3 INTENSITY OF ADVERSE EVENT ..................................................................................................................53
10.4 CAUSALITY ASSESSMENT............................................................................................................................54
10.5 ACTION TAKEN WITH THE STUDY DRUG DUE TO AN ADVERSE EVENT.......................................................54
10.6 OTHER ACTIONS TAKEN..............................................................................................................................54
10.7 OUTCOME....................................................................................................................................................55
10.8 RECORDING ADVERSE EVENTS ...................................................................................................................55
10.9 REPORTING SERIOUS ADVERSE EVENTS TO CHIESI.....................................................................................56
10.10 REPORTING SERIOUS ADVERSE EVENTS TO REGULATORY AUTHORITIES/ETHICS COMMITTEE................56
10.11 GENERAL NOTES.......................................................................................................................................56
11.
DATA MANAGEMENT.............................................................................................................................57
12.
STATISTICAL METHODS.......................................................................................................................58
12.1 SAMPLE SIZE...............................................................................................................................................58
12.2 ANALYSIS SETS...........................................................................................................................................58
12.3 STATISTICAL ANALYSIS ..............................................................................................................................59
13.
ETHICS COMMITTEE .............................................................................................................................63
14.
REGULATORY REQUIREMENTS.........................................................................................................63
15.
INFORMED CONSENT.............................................................................................................................64
16.
SOURCE DOCUMENTS/DATA...............................................................................................................64
16.1 RECORDING OF SOURCE DATA....................................................................................................................64
16.2 DIRECT ACCESS TO SOURCE DOCUMENT/DATA..........................................................................................64
17.
STUDY MONITORING.............................................................................................................................65
18.
QUALITY ASSURANCE...........................................................................................................................65
19.
INSURANCE AND INDEMNITY.............................................................................................................65
20.
CONFIDENTIALITY.................................................................................................................................66
21.
PREMATURE TERMINATION OF THE STUDY ................................................................................66
22.
CLINICAL STUDY REPORT...................................................................................................................66
23.
RECORD RETENTION.............................................................................................................................66
24.
PUBLICATION OF RESULTS.................................................................................................................66
25.
REFERENCES ............................................................................................................................................68
APPENDIX 1 - APPROVAL OF THE PROTOCOL BY COORDINATING CLINICAL 
INVESTIGATOR..................................................................................................................................................71
APPENDIX 2 - APPROVAL OF THE PROTOCOL BY CLINICAL INVESTIGATOR(S).......................72
APPENDIX 3 - RECOMMENDATIONS RELATED TO CONTRACEPTION AND PREGNANCY 
TESTING IN CLINICAL STUDIES ..................................................................................................................73






Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 19/73
2.
STUDY OBJECTIVES
2.1 Primary Objective
The primary objective is to assess the safety and tolerability of single ascending doses of 
CHF10067 in subjects with IPF.
2.2 Secondary Objectives
The secondary objectives are:
to evaluate the CHF10067 PK profile in serum 
to evaluate the CHF10067 immunogenicity profile in terms of ADA and neutralising 
antibody (nAb). 
2.3 Exploratory Objective
The exploratory objective is to evaluate TG2 levels in plasma.
3.
STUDY DESIGN 
This is a Phase Ib, multi-centre, multi-country, randomised, double-blind, placebo-controlled 
study to investigate the safety, tolerability, immunogenicity, and PK of single IV doses of 
CHF10067 in subjects with IPF. The effect of CHF10067 on TG2 levels will also be 
investigated as an exploratory endpoint.
Overall, 24 subjects will be studied in 3 cohorts (Cohorts A [1000 mg], B [anticipated 
2000 mg], and C [anticipated 3000 mg]) consisting of 8 subjects per cohort. In each cohort, 
6 subjects will receive CHF10067, and 2 subjects will receive placebo.
The doses will be administered according to an escalation scheme designed to ensure sufficient 
safety conditions for subjects. In each cohort, subjects will be divided into 2 sub-groups, with 
each sub-group being dosed at least 24 hours apart. The first sub-group will comprise 2 subjects, 
with 1 subject receiving CHF10067 and 1 subject receiving placebo. The second sub-group will 
comprise 6 subjects, with 5 subjects receiving CHF10067 and 1 subject receiving placebo. 
Continuation to dose the remaining 6 subjects will be evaluated by at least the Medical Monitor 
and Sponsor Clinical Research Physician based on the safety data provided by the 
Investigator(s) where the first-sub-group have been dosed. The decision to escalate to the next 
dose will be made by the Safety Advisory Committee when safety data until Day 14 have been 
collected for all subjects at the previous dose level. Pharmacokinetic and immunogenicity data 
will also be included in the safety evaluation for dose escalation (if available) but are not 
mandatory to escalate to the next dose. Further details regarding dose escalation are provided 
in Section 6.2.2.1.
The screening visit will take place between 3 to 28 days prior to randomisation and subject 
eligibility will be assessed according to the inclusion/exclusion criteria. The signed informed 
consent form (ICF) will be obtained prior to any study-related procedures. 


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 20/73
On Day 1, subjects will attend the clinical site for an ambulatory visit. Following confirmation 
of eligibility, subjects will be randomised to either CHF10067 or placebo and will receive a 
single IV dose of CHF10067 or placebo. 
Subjects will be monitored for safety, tolerability, immunogenicity, PK, and TG2 levels for 
84 days post-dose and will attend ambulatory visits on Days 2, 5, 7, 14, 28, 56, and 84 (end of 
study). The total duration of participation is expected to last approximately 16 weeks. The end 
of the study is defined as the last visit of the last subject in the study. Even if not mandatory, 
overnight stay is always possible for logistical reasons or to accomplish site/subject preferences.
An overview of the study design is shown in Figure 1. 
Figure 1: Study Design
4.
SUBJECT SELECTION CRITERIA
4.1 Subject Recruitment
Overall, 24 subjects will be studied in 3 cohorts (Cohorts A, B, and C), consisting of 8 subjects 
per cohort. In each cohort, 6 subjects will receive CHF10067, and 2 subjects will receive 
placebo. In each cohort, a minimum of 2 subjects are required to be not receiving antifibrotic 
treatment (including subjects with previous use of antifibrotic treatment that has been stopped 
for at least 2 weeks prior to screening).
4.2 Inclusion Criteria 
Subjects must meet all the following inclusion criteria to be eligible for enrolment into the 
study: 
1.
Subject’s written informed consent obtained prior to any study-related procedure.
2.
Males or females, of any race, aged ≥ 40 years of age.
3.
Body mass index (BMI) between 18.0 and 35.0 kg/m2, inclusive.
4.
Body weight ≥ 45 kg.


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 21/73
5.
Diagnosis of IPF as defined by current ATS/ERS/JRS/ALAT guidelines (2022) which 
will include patients with an usual interstitial pneumonia (UIP) pattern or probable UIP 
pattern with confirmation of IPF diagnosis based on the Multi-Disciplinary Team 
Discussion (excluding other possible etiological causes of the high-resolution 
computed tomography [HRCT] pattern). Where a lung biopsy is available, the 
computerized tomography (CT) pattern and biopsy results must be compatible with a 
diagnosis of IPF.[1]
Diagnosis of IPF must be within the past 5 years prior to enrolment, and in the opinion 
of the Investigator, has been stable for at least 3 months.
6.
Subjects not receiving any IPF treatment (including subjects with previous use of 
antifibrotic treatment that has been stopped for at least 2 weeks prior to screening) or 
receiving well-tolerated standard of care approved treatments at a stable dose for at 
least 8 weeks prior to screening (nintedanib or pirfenidone) and it is anticipated the 
dose will remain unchanged throughout the study.
7.
Oxygen saturation ≥ 92% at rest by pulse oximetry while breathing ambient air at 
screening and prior to randomization.
8.
Forced vital capacity (FVC) ≥ 50% of predicted and ratio of forced expiratory volume 
in the first second (FEV1)/FVC ≥ 0.7 at screening.
9.
Diffusing capacity of the lung for carbon monoxide (DLCO; corrected for haemoglobin) 
≥ 35% at screening.
10. Able to understand the study procedures and the risks involved.
11. Female subjects: 
a.
Women of childbearing potential (WOCBP) fulfilling 1 of the following 
criteria: 
i. WOCBP with fertile male partners: they and/or their partner must be 
willing to use a highly effective birth control method preferably with 
low user dependency from the signature of the informed consent and 
until the last study visit or
ii. WOCBP with non-fertile male partners: contraception is not required 
in this case. 
Or
b. Female subjects of non-childbearing potential defined as physiologically 
incapable of becoming pregnant (i.e., post-menopausal or permanently sterile, 
as per definitions given in APPENDIX 3). Tubal ligation or partial surgical 
interventions are not acceptable. If indicated, as per Investigator’s request, 
post-menopausal status may be confirmed by screening serum follicle-
stimulating hormone levels (according to local laboratory ranges). 
12.  Males fulfilling one of the following criteria: 


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 22/73
a.
Males with pregnant or non-pregnant WOCBP partners: they must be willing 
to use male condom from the signature of the informed consent and until the 
last study visit or 
b. Non-fertile male subjects: contraception is not required in this case or
c.
Males with partner not of childbearing potential: contraception is not required 
in this case.
For the definition of WOCBP, fertile men, and the list of highly effective birth control methods 
with low user dependency see APPENDIX 3 or Section 4.1 of the Clinical Trial Facilitation 
Group guidance [16]. 
The following inclusion criteria should be re-checked at the Day 1 visit (prior to randomisation): 
7.
4.3 Exclusion Criteria
The presence of any of the following will exclude a subject from study enrolment: 
1.
History of lower respiratory tract infection within 4 weeks prior to screening and up to 
Day 1 of the study, which required the use of antibiotics and admission to a clinical 
facility, or community treated lower respiratory tract infection that in the opinion of 
the investigator would preclude the subject’s participation in the study.
2.
History of acute exacerbation of IPF within 3 months prior to screening and up to Day 1 
of the study, defined as:
a.
worsening or newly developed dyspnoea as reported by the subject (≤ 30 days)
b. new bilateral ground-glass opacities on HRCT superimposed on the UIP 
abnormalities that defined subject eligibility for the study, and
c.
worsening hypoxemia (in the judgment of the Investigator), in the absence of 
pulmonary infection, heart failure, or other identifiable causes for this finding.
3.
Planned surgery during the study.
4.
Active diagnosis of lung cancer or a history of lung cancer.
5.
Active cancer or a history of cancer (other than lung cancer) with less than 5 years 
disease free survival time (whether or not there is evidence of local recurrence or 
metastases). Localised carcinoma (e.g., basal cell carcinoma or in situ carcinoma of the 
cervix adequately treated, etc.) is acceptable. 
6.
Infiltrative lung disease other than IPF, including any of the following:
a.
Other types of idiopathic interstitial pneumonias [17] 
b. Interstitial lung diseases related to exposure to fibrogenic agents, other 
environmental toxins, or drugs
c.
Other types of occupational lung diseases


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 23/73
d. Granulomatous lung diseases
e.
Pulmonary vascular diseases
f.
Related to systemic diseases (including vasculitis and connective tissue 
diseases).
7.
History of other types of respiratory diseases in the opinion of the Investigator, would 
impact the endpoints in the protocol or otherwise preclude the subject’s participation 
in the study including diseases or disorders of the airways, lung parenchyma, pleural 
space, mediastinum, diaphragm, or chest wall.
8.
End-stage fibrotic disease expected to require organ transplantation within 6 months.
9.
Trauma or surgical procedures requiring hospitalisation within 4 weeks prior to 
screening visit.
10. Subjects exhibiting unhealed wounds or foot ulcers or have known history of wound 
healing complications. 
11. Clinically relevant and uncontrolled cardiac, hepatic, gastrointestinal, renal, endocrine, 
metabolic, neurologic, or psychiatric disorders that may interfere with successful 
completion of this protocol according to the Investigator's judgment.
12. Any abnormal and clinically significant 12-lead electrocardiogram (ECG) that in the 
Investigator's opinion would affect safety evaluation or place the subjects at risk at 
screening and prior to randomization. 
13. Chronic heart failure categorized as New York Heart Association Class II, III, or IV 
(this applies to symptoms of chronic heart failure, not IPF); clinical diagnosis of cor 
pulmonale requiring specific treatment; or severe pulmonary hypertension requiring 
specific treatment that, in the opinion of the Investigator, would preclude the subject’s 
participation in the study.
14. Currently receiving, or have received, a systemic corticosteroid, immunosuppressant, 
cytotoxic therapy, vasodilator therapy for pulmonary hypertension, or unapproved or 
investigational treatment for IPF within 4 weeks prior to screening or prior to 
randomization. Treatment with pirfenidone or nintedanib, though not both 
concurrently, is permitted, provided that the subject has been on a well-tolerated stable 
dose for at least 8 weeks prior to screening and it is anticipated the dose will remain 
unchanged throughout the study.
15. Participation in another clinical study with an investigational drug in the 1 month or 
5 half-lives of that investigational drug (whichever is longer) preceding dosing; a 
longer and more appropriate time could be considered by the Investigator based on the 
elimination half-life and/or long-term toxicity of the previous investigational drug.
16. Received the coronavirus disease-2019 (COVID-19) vaccine ≤ 7 days before dosing. 
 Any systemic symptoms (e.g., myalgia, fever, chills, fatigue, etc.) after COVID-19 
vaccine should subside at least 2 days before the Day 1 visit.
17. Any other drugs which may interfere with the safe completion of the study, according 
to the Investigator opinion, are also forbidden. 


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 24/73
18. Presence of any current infection, or previous infection that resolved less than 7 days 
prior to screening or before treatment (with the exception of lower respiratory tract 
infections, for which the exclusion criterion is defined separately: exclusion criterion 
n. 1).
19. Documented coronavirus disease-2019 (COVID-19) diagnosis within the last 4 weeks 
or which has not resolved within 7 days prior to screening or before treatment. COVID-
19 testing prior to enrolment and during the study will be conducted according to 
current local guidelines and is not specified in the protocol. 
20. Known intolerance and/or hypersensitivity to any of the excipients contained in the 
formulation or any other substance used in the study.
21. History of allergic or anaphylactic reaction to human, humanised, chimeric, Igs, or 
murine monoclonal antibodies.
22. History of severe episodes of urticaria and angioedema or diagnosis of chronic urticaria 
and its underlying disorders including, but not limited to acquired angioedema due to 
C1-inhibitor deficiency, auto-inflammatory disease, hereditary angioedema, or 
urticarial vasculitis.
23. Confirmed or suspected diagnosis of mastocytosis.
24. Clinically relevant abnormal laboratory values (clinical chemistry and haematology) 
at screening suggesting an unknown disease and requiring further clinical investigation 
or which may impact the safety of the subject or the evaluation of the study results 
according to Investigator judgement. Note: in case of abnormal laboratory values, that 
could indicate a temporary condition, the test can be repeated twice before 
randomisation.
25. Positive human immunodeficiency virus (HIV) 1 and/or HIV2 results at screening.
26. Positive hepatitis result that indicates acute or chronic hepatitis B (HB) or hepatitis C 
(HC) at screening (i.e., positive HB surface antigen, HB core antibody [IgM anti-HB 
core antibody], or HC antibody).
27. Blood donation or blood loss (equal or more than 450 mL) within 2 months prior to 
screening or prior to randomization.
28. History of cigarette (or e-cigarette) smoking or use of nicotine- or tobacco-containing 
products within 3 months prior to screening or a positive urine test for cotinine at 
screening. 
29. Documented history of alcohol abuse within 12 months prior to screening or a positive 
alcohol breath test prior to randomization. Note: before randomization, the test can be 
repeated once, at least 3 days after the last positive test, if the Investigator evaluates 
that the subject will be compliant to alcohol abstinence during the study.
30. Documented history of drug abuse within 12 months prior to screening or a positive 
urine drug screen prior to randomization. Note: before randomization, the test can be 
repeated once at least 15 days after the last positive test, if the Investigator evaluates 
that the subject will be compliant to drug abstinence during the study.


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 25/73
31. Unsuitable veins for repeated venipuncture.
32. Pregnant or lactating women, where pregnancy is defined as the state of a female after 
conception and until termination of the gestation, confirmed by a positive serum human 
chorionic gonadotropin laboratory test. A serum pregnancy test will be performed at 
screening and urine pregnancy test will be performed prior to randomisation.
The following exclusion criteria should be re-checked at the Day 1 visit (prior to 
randomisation): 1, 2, 12, 14, 18, 19, 27, and 32. 
Re-testing is possible as explicated in the relative notes of the inclusion/exclusion criteria list.
Screening failure subjects due to the presence of a temporary conditions (e.g., lower respiratory 
tract infections, unhealed wound, etc.) defined in the exclusion criteria list could be re-screened 
only once if the condition is resolved according to Investigator’s opinion. 
Rescreened participants should be assigned a new subject number and the rescreening 
procedure can be done only once.
4.4 Subject Withdrawals
Subjects must be discontinued from the study for any of the following reasons:
An adverse event (AE) occurs that, in the opinion of the Investigator, makes it unsafe for 
the subject to continue in the study. In this case, the appropriate measures will be taken. 
The subject meets the individual stopping criteria.
The subject is lost to follow-up.
The subject withdraws consent.
The subject's safety is affected by violation of inclusion or exclusion criteria or use of 
not-permitted concomitant medication.
The subject, in the opinion of the investigator, is unwilling or unable to adhere to the 
study requirements, i.e., non-compliance.
The Sponsor or the regulatory authorities or the Ethics Committees (ECs), for any reason, 
terminates the entire study, or terminates the study for this study site or this particular 
subject. 
It is understood by all concerned that an excessive rate of withdrawals can render the study 
uninterpretable; therefore, unnecessary withdrawals of subjects should be avoided. However, 
should a subject discontinue the study, all efforts will be made to complete the Early 
Termination procedures and report the observations as thoroughly as possible.
In the event of early termination, if the subject has not withdrawn his/her consent, an Early 
Termination visit should be scheduled to perform the following safety assessments, as described 
in section 7.1.3.


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 26/73
In case of withdrawal, the Investigator must fill in the “Study Termination” page in the 
electronic case report form (eCRF), reporting the main reason for withdrawal. Subjects who 
discontinue will be replaced in order to ensure that at least 8 evaluable subjects in each dose 
level complete the Day 14 study assessments. In case the discontinuation is due to safety reasons 
assessed as related to the study drug, the subject will not be replaced.
If a subject is withdrawn/drops-out of the study after receiving the test treatment, the subject 
study number and corresponding test treatments should not be reassigned to another subject.
5.
CONCOMITANT MEDICATIONS
5.1 Permitted Concomitant Medications
The following concomitant medications are permitted during the study: 
1. Well-tolerated standard of care treatment of IPF (nintedanib or pirfenidone) at stable 
doses for at least 8 weeks prior to screening and not expected to change during the 
study. Concomitant intake of both nintedanib and pirfenidone is not allowed. 
2. COVID-19 vaccine at least 7 days before dosing. Note: Any systemic symptoms (e.g., 
myalgia, fever, chills, fatigue, etc.)  after COVID-19 vaccine should subside at least 2 
days before the treatment visit.
3. Hormone replacement therapy, oral, implantable, transdermal, injectable, or 
intravaginal contraceptives. 
5.2 Non-permitted Concomitant Medications
The following concomitant medications are not permitted during the study: 
1. Systemic corticosteroids 
2. Immunosuppressants
3. Cytotoxic therapy or vasodilator therapy for pulmonary hypertension
4. Any other unapproved or investigational treatment for IPF
5. Any other drug which may interfere with the safe completion of the study, according to 
the Investigator's opinion, is also forbidden.
In case of exacerbations, appropriate medications can be initiated at Investigator’s discretion.
6.
TREATMENT(S)
CHF10067 and placebo (study treatments) will be supplied to the clinical site under the 
responsibility of the Sponsor, who will also provide the Pharmacist/Investigator with 
appropriate certificates of analytical conformity and Qualified Person release. The placebo 
solution 
 will 
be supplied by the Sponsor as described within the investigational medicinal product (IMP) 
Pharmacy Manual. 




Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 28/73
Continuation to dose the remaining 6 subjects will be evaluated by at least the Medical Monitor 
and Sponsor Clinical Research Physician based on the safety data (e.g., AE profile) provided 
by the Investigator(s) where the first sub-group have been dosed. The procedure for 
communication and initiation of dosing the remaining subjects within each cohort will be 
clearly detailed in a separate charter.
The decision to escalate to the next dose will be made by the Safety Advisory Committee when 
safety data until Day 14 have been collected for all subjects at the previous dose level. 
Pharmacokinetic and immunogenicity data will also be included in the safety evaluation for 
dose escalation (if available) but are not mandatory to escalate to the next dose.
The Safety Advisory Committee will comprise at least the Coordinating Investigator, Medical 
Monitor, Sponsor’s representatives (these may also include Key Opinion Leaders), and site 
Investigators identified from some of the enrolling sites. The presence of all site-Investigators 
is not mandatory. This committee will be governed by a separate charter.
A blinded interim safety report, summarising results from all available safety assessments for 
each subject, as specified above, will be sent by the Investigator(s) and appropriately blinded 
PK and immunogenicity data (if available) will be sent by the appropriate parties to the Sponsor 
and Safety Advisory Committee prior to the start of each successive group. Unblinding during 
the interim review may occur in certain situations, if necessary to take an informed decision, 
and will be clearly detailed in a separate charter. 
A Safety Advisory Committee meeting will occur prior to each dose escalation. In particular, 
any clinically significant results will be discussed before dose escalation continues. 
The decision to dose-escalate will be a unanimous decision between the Sponsor, Medical 
Monitor, and the Coordinating Investigator. If either the Sponsor or the Coordinating 
Investigator considers stopping of dose escalation to be appropriate, dose escalation will be 
terminated. 
Study drug will be discontinued in any individual subject that experiences a drug-related serious 
AE (SAE) or any other AE that, in the opinion of the Coordinating Investigator or site 
Investigator, warrants discontinuation of study drug.
Doses will not be further escalated if:
Two or more subjects on active drug* experience a possibly drug-related SAE
Two or more subjects on active drug* experience a severe, possibly drug-related AE 
lasting for > 24 hours duration
Four or more subjects on active drug* experience at least moderate, possibly drug-related 
AE in the same Medical Dictionary for Regulatory Activities (MedDRA) System Organ 
Class of > 24 hours duration


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 29/73
Despite the above criteria not being met, a pattern of AEs has emerged that leads the 
Investigator and/or Safety Advisory Committee to believe that dose escalation is not 
justifiable on safety grounds. 
* Unblinding is possible to take an informed decision before stopping the dose escalation, as 
detailed in the separate charter.
6.2.2.2 Background medication
Subjects may take permitted concomitant medications allowed by protocol, but these will not 
be provided by the Sponsor. 
6.2.3 Preparation of the study drug
The preparation of the final concentration will be performed in the Laminar Air Flow Bench or 
other sterile dedicated preparation area using aseptic procedures under unblinded conditions.
The components of the IMP 
 and the 
various items of equipment (infusion bags, lines, syringes, needles, etc.) are all provided in an 
internally sterile state, in common with such items in routine clinical use. In keeping with best 
medical practice, the minimum standards that should be applied in the preparation of IMP for 
administration are those that would be used for the preparation of any other medicinal product 
for IV administration, to minimise the possibility of pathogenic contamination of the contents 
and equipment:
Use of new (previously un-used), freshly-opened materials
Use of a “sterile” (no-touch) technique
Preparation and use in a clean, dust-free environment.
In case of any mistakes during the study drug preparation, a new study drug will be prepared 
using new material.
The list of the components for dose preparation (dilution) and dose administration together with 
detailed instructions for the preparation and dilution of CHF10067 and placebo are provided in 
the IMP Pharmacy Manual.
6.2.4 Administration
No fluid or diet restrictions are required prior treatment administration.
Treatment administration must be completed within 10 hours from the removal of the product 
from the fridge. Doses will be administered as follows: 
Cohort A: Single doses of 1000 mg CHF10067 or placebo will be administered as an IV 
infusion. 






Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 32/73
dispense after these dates. The IRT will monitor inventory levels at all sites and manage the 
study treatment re-supply. 
The randomisation list will be provided to the labelling facility and to the PK/immunogenicity 
laboratory but will not be available to subjects, Investigators, or employees of the site involved 
in the management of the study before unblinding of the data (unless in case of emergency) with 
the following exceptions:
Unblinded Site Pharmacist(s) or the designated/authorised representative involved in IMP 
preparation and dispensing and identified in the appropriate delegation log
Unblinded Monitor(s) who review(s) the IMP-related documentation
Unblinded bioanalytical laboratory staff involved in the analysis of PK/immunogenicity 
samples.
The Sponsor’s clinical team will also be blinded during the study as they will not have direct 
access to the randomisation list.
In case of emergency, where the Investigator considers essential to know what treatment the 
subject was taking, unblinding of the treatment code will be done through IRT and the treatment 
group will be disclosed. The IRT will be designed to send a confirmation (by notification email) 
to the site for every transaction performed by the Investigators, including unblinding. The IRT 
will also promptly notify the Sponsor and the Clinical Monitor whenever a treatment code is 
unblinded. The procedure for unblinding before stopping dose escalation will be described in a 
separate charter. 
Users from Chiesi Global Pharmacovigilance will have their own credentials to unblind 
subjects in case of Suspected Unexpected Serious Adverse Reactions (SUSARs) to be reported 
to the competent Regulatory Authorities and ECs/Institutional Review Boards. 
6.7 Treatment Compliance
For each subject, details of study medication intake will be recorded in the eCRF. 
6.8 Drug Storage 
The unblinded Pharmacist at the Investigator’s site will be responsible for the safe storage of 
all medications assigned to this study, in a secure place with restricted access limited to those 
individuals authorised to dispense the treatment and maintained within the appropriate ranges 
of temperature.
All CHF10067 kits will be stored at refrigerated temperatures at 2°C to 8°C. Placebo will be 
stored not above 30°C. The IMP Pharmacy Manual will contain additional information for 
temperature condition before and after the preparation. 
For the study treatments, the maximum cumulated hold time from the removal of product from 
the fridge to the end of infusion is 10 hours. 


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 33/73
A summary of the holding times to be applied will be detailed in the IMP Pharmacy Manual.
6.9 Drug Accountability
The Pharmacist, or the designated/authorised representative, is responsible for the management 
of all the study treatments to be used for the study. Study treatments should be stored in a 
locked, secure storage facility with access limited to those individuals authorised to dispense 
the study treatments.
An inventory will be maintained by the Pharmacist (or other designated individual), to include 
a signed account of all the study treatments received and dispensed during the study. 
At the conclusion or termination of the study, the Investigator or the Pharmacist shall conduct 
and document a final drug supply (used and unused) inventory. An explanation will be given 
for any discrepancies.
All the study treatments supplied, used or unused, will be returned to the designated distributor 
centre to be destroyed centrally. The return of study treatments will occur only after full 
accountability and reconciliation are completed. The study treatments destruction will not occur 
until authorised by Chiesi.
6.10 Provision of Additional Care
At completion of subject’s study participation, it is under the Investigator’s responsibility to 
prescribe the more appropriate treatment for the subject or to restore the initial therapy or to 
refer to the General Practitioner.


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 34/73
7.
STUDY PLAN
7.1 Study Schedule – All Cohorts
Treatment Period
Early 
Termination
Screening 
(Days -28 
to -3)
Day 1
Day 2
Days 5 
and 7 (± 
1 day)
Days 14, 
28, and 56 
(± 2 days)
Day 84 
(± 2 
days)
Informed consent
X
Randomisation
X
Ambulatory visit
X
X
X
X
X
X
X
Treatment Intake
CHF10067 or placebo 
administration a
X
Subject Health Evaluation
In/Ex criteria
X
X b
Medical history
X
Demographic data
X
Height and weight
X
Alcohol breath test
X
Physical examination
X
X
X
X
X
Abbreviated physical 
examination 
X
X
Adverse events recording
X
X
X
X
X
X
X
Restrictions
X
X
X
X
X
X
Concomitant medication
X
X
X
X
X
X
X
Safety Assessment in Blood
Fasting clinical chemistry
X
X
(pre-dose)
X
X h
X
X
X
Haematology
X
X
(pre-dose)
X
X h
X
X
X
Fasting glucose
X
X
(pre-dose)
X
X h
X
X
X
FSH (post-menopausal 
female subjects) and/or 
pregnancy test (females of 
childbearing potential)
X
Serology
X
Markers for evaluation of 
immediate hypersensitivity 
reactions
X f
ADA and nAb (in case of 
positive ADA)
X
(pre-dose)
X
X
X
Other Assessments
TG2 levels
X
(pre-dose)
X
X
Naso-absorption samples
X
(pre-dose)
X i
Proteomic sample (serum)
X
(pre-dose)
X i
Proteomic sample (plasma)
X
(pre-dose)
Optional transcriptomic 
samples
X
(pre-dose)
X i
Assessments in Urine
Urinalysis
X
Drug screen
X


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 35/73
Treatment Period
Early 
Termination
Screening 
(Days -28 
to -3)
Day 1
Day 2
Days 5 
and 7 (± 
1 day)
Days 14, 
28, and 56 
(± 2 days)
Day 84 
(± 2 
days)
Cotinine
X
Pregnancy test (females of 
childbearing potential)
X
X j
X
Pharmacokinetic in Blood c
CHF10067
X
X
X
X
X
Safety Cardiac Assessments 
Vital signs d
X
X
X
X
X
X
X
Local 12-lead ECG e
X
X
X
X
X
X
X
Safety Pulmonary 
Assessments 
Oxygen saturation g
X
X
X
X
X
X
X
Spirometry
X
X k
X k
X
X
Diffusing capacity
X
X l
X
X
Abbreviations: ADA = anti-drug antibody; ECG = electrocardiogram; FSH = follicle-stimulating hormone; In/Ex = 
inclusion/exclusion; nAb = neutralising antibody; TG2 = transglutaminase 2. 
Footnotes for Evaluation Schedule: 
a Special attention will be given to immediate hypersensitivity reactions and monitoring up to 8 hours post-dose is required. If 
the subject has no symptoms, he/she can be discharged. If the subject has symptoms, he/she may remain overnight. An overnight 
stay is also permitted for logistical reasons and/or site’s/subject’s preference. 
b Specific In/Ex criteria will also be checked pre-dose on Day 1 according to study schedule and In/Ex criteria. 
c Pharmacokinetic blood samples for serum CHF10067 will be collected at the following timepoints: pre-dose (within 
75 minutes from start of infusion), at the end of infusion, and 2, 4, 8, and 20 hours after the end of the infusion and 5, 7, 14, 
28, 56 and 84 days post-dose.
d Vital signs (blood pressure, pulse rate, respiratory rate, body temperature): systolic and diastolic blood pressure will be 
evaluated in duplicate after 5 minutes in supine position. Vital signs will be measured at screening and at the following 
timepoints: pre-dose, every 15 minutes during the infusion (e.g., 15, 30, 45, 60, 75, 90, 105, etc.), at the end of the infusion and 
30 min, 1, 2, 3, 4, 6, 8, and 20 hours after the end of the infusion and 5, 7, 14, 28, 56, and 84 days post-dose.
e Local 12-lead ECG: a triplicate ECG will be performed to assess eligibility and a single ECG will be evaluated at all other 
timepoints. Electrocardiograms will be measured at screening and at the following timepoints: pre-dose on Day 1, and Days 2, 
7, 28, and 84.
f Markers for evaluation of immediate hypersensitivity reactions: pre-dose for all subjects. If required (based on subject 
experiencing symptoms of immediate hypersensitivity reactions), blood samples will be collected at 1 and 2 hours after the 
onset of the event.
g Oxygen saturation: will be measured at screening and continuous monitoring will occur from pre-dose to 10 hours post-
dose at the following timepoints: pre-dose, every 15 minutes during the infusion (e.g., 15, 30, 45, 60, 75, 90, 105, etc.), at 
the end of the infusion and 30 min, 1, 2, 3, 4, 6, 8, hours after the end of infusion. Oxygen saturation will also be measured 
at 20 hours after the end of infusion, and 5, 7, 14, 28, 56 and 84 days post-dose.
h Clinical laboratory evaluations will be conducted on Day 7 only. 
i Sample(s) will be collected on Day 14 only.
j Pregnancy test conducted on Days 28 and 56.
k Spirometry conducted on Days 7, 28, and 56 only. 
l Diffusing capacity conducted on Days 28 and 56 only.
7.1.1 Screening
A screening visit will take place between 3 to 28 days prior to randomisation to identify eligible 
consenting subjects for the study. 


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 36/73
The signed written INFORMED CONSENT by potential eligible subjects will be collected, 
after the study has been fully explained by the Investigator or designee. The Investigator or 
his/her designee should provide the subjects ample time and opportunity to inquire about details 
of the study and to decide whether or not to participate in the study. If the subject agrees to 
participate, the signed and dated informed consent must be obtained before any below study 
related procedures. If the restrictions and/or the fasting are not respected, the visit should be 
rescheduled. 
The following procedures will take place:
SUBJECT SELECTION: Inclusion/exclusion criteria will be checked. 
MEDICAL/SURGICAL HISTORY AND CONCOMITANT DISEASES: Subject health 
history will be recorded.
DEMOGRAPHY DATA COLLECTION: Demographic data including age, sex, and 
race, will be recorded.
HEIGHT AND WEIGHT: Will be recorded.
ALCOHOL BREATH TEST: Will be performed.
PHYSICAL EXAMINATION: A comprehensive physical examination will be 
performed according to Section 7.2.10.
ADVERSE EVENTS RECORDING: Adverse events occurred since the signature of the 
informed consent will be recorded. In case of any clinically significant abnormality 
revealed during the physical examination or screening procedures, it will be recorded in 
the subject’s medical history, unless its start date/time is after the informed consent 
signature date/time and it is not due to a pre-existing condition. In the latter case, it will 
be recorded as an AE.
STUDY RESTRICTIONS: Study restrictions criteria will be checked according to 
section 7.1.4.
PRIOR AND CONCOMITANT MEDICATIONS CHECK: Any systemic corticosteroid, 
immunosuppressant, cytotoxic therapy, vasodilator therapy for pulmonary hypertension, 
or unapproved or investigational treatment for IPF within 4 weeks prior to screening will 
be recorded.  Any other drug which may interfere with the safe completion of the study 
will also be recorded. Permitted treatment with pirfenidone or nintedanib will also be 
recorded.
BLOOD TESTING: Blood sample collection for safety evaluations (clinical chemistry, 
haematology, serology, fasting glucose), pregnancy (females of childbearing potential), 
and FSH (post-menopausal female subjects) testing according to Sections 7.2.2.1 to 
7.2.2.3. Subjects have to be in fasting condition from at least 10 hours before clinical 
chemistry and fasting glucose samples are collected.
URINE TESTING: Urine sample collection for urinalysis, drug screen and cotinine test 
will occur according to Section 7.2.6.
VITAL SIGNS: Measurement of systolic and diastolic blood pressure, pulse rate, 
respiratory rate, and body temperature according to Section 7.2.8.


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 37/73
LOCAL ECG: Triplicate 12-lead ECG will be used to measure heart rate, PR, QRS, and 
QT corrected for heart rate by Fridericia's formula (QTcF) according to Section 7.2.9.
PULMONARY ASSESSMENTS: Oxygen saturation, Spirometry (FEV1, FEV1 % of 
predicted normal and lower limit of normal value, FVC, FVC% of predicted normal and 
lower limit of normal value, and FEV1/FVC), , and diffusing capacity (DLCO [unadjusted], 
DLCO % predicted, DLCO corrected for haemoglobin, DLCO corrected for haemoglobin % 
predicted, carbon monoxide transfer coefficient [KCO], and alveolar volume [VA]) will 
be measured according to Section 7.2.7.
7.1.2 Treatment period
The subject will attend ambulatory visits on Days 1, 2, 5, 7, 14, 28, 56, and 84 (end of study).
The following procedures will take place during the treatment period: 
SUBJECT SELECTION (Day 1 visit): Inclusion criteria no. 7 and exclusion criteria no. 
1, 2, 12, 14, 18, 19, 27, and 32 will be re-checked as requested in Sections 4.2 and 4.3. 
Subjects not fulfilling the mentioned criteria will be screen failed. 
RANDOMISATION (Day 1 visit): Subjects will be randomised to receive a single IV 
dose of CHF10067 or placebo. 
DOSING (Day 1 visit): Subjects will be administered a single IV dose of CHF10067 or 
placebo. 
PHYSICAL EXAMINATION (Day 1, 2, 5, and 7 visits): A full physical examination 
will be performed according to Section 7.2.10 and any new revealed clinically significant 
abnormality since the last visit will be recorded as an AE.
ABBREVIATED PHYSICAL EXAMINATION (Day 14, 28, 56, and 84 visits): A 
symptom-directed physical examination will be performed according to Section 7.2.10 
and any new revealed clinically significant abnormality since the last visit will be 
recorded as an AE.
ADVERSE EVENTS RECORDING (all visits): Any new AE/SAE occurred since the 
last visit will be checked and recorded in the eCRF. The status of ongoing AEs will be 
checked and updated in the eCRF when applicable. Moreover, during this period in case 
of any new clinically significant abnormality revealed during the examination or 
procedures, it will be recorded as an AE.
STUDY RESTRICTIONS (all visits): Study restrictions criteria will be checked 
according to section 7.1.4.
CONCOMITANT MEDICATIONS CHECK (all visits): Concomitant medications taken 
by the subject since the last visit will be checked and recorded in the eCRF.
BLOOD TESTING: Blood sample collection for safety evaluations (clinical chemistry, 
haematology, fasting glucose [Day 1 pre-dose, 2, 7, 14, 28, 56, and 84 visits], 
immunogenicity [Day 1 pre-dose, 14, 28, 56, and 84 visits], and markers for evaluation 
of immediate hypersensitivity reactions [Day 1 visit]) according to Sections 7.2.2.1, 


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 38/73
7.2.2.4 and 7.2.2.5. Subjects have to be in fasting condition from at least 10 hours before 
clinical chemistry and fasting glucose samples are collected.
URINE TESTING: Urine samples for pregnancy testing (females of childbearing 
potential [Day 1, 28, 56, and 84 visits]) will occur according to Section 7.2.6
PHARMACOKINETIC INVESTIGATION (all visits): Collection of blood for PK 
assessment according to Section 7.2.1.
VITAL SIGNS (all visits): Measurement of systolic and diastolic blood pressure, pulse 
rate, respiratory rate, and body temperature according to Section 7.2.8.
LOCAL ECG (Day 1, 2, 7, 28, and 84 visits): Single 12-lead ECG will be used to 
measure heart rate, PR, QRS, and QTcF according to Section 7.2.9.
PULMONARY ASSESSMENTS: Oxygen saturation (all visits), Spirometry (Day 7, 28, 
56, and 84 visits); FEV1, FEV1 % of predicted normal and lower limit of normal value, 
FVC, FVC% of predicted normal and lower limit of normal value, FEV1/FVC, and 
diffusing capacity (Day 28, 56, and 84 visits); DLCO (unadjusted), DLCO % predicted, DLCO 
corrected for haemoglobin, DLCO corrected for haemoglobin % predicted, KCO, and VA) 
will be measured according to Section 7.2.7.
TG-2 ASSESSMENT (Day 1, 14, 28, 56, and 84 visits): Transglutaminase 2 levels in 
plasma will be measured according to Section 7.2.3.
NASO-ABSORPTION SAMPLES (Day 1 and Day 14 visits): Two mucosal samples 
(one from each nostril) will be taken at each timepoint according to Section 7.2.5.
SERUM PROTEOMIC SAMPLE (Day 1 and Day 14 visits): A blood sample for serum 
proteomic analysis will be taken at each timepoint according to Section 7.2.4. 
PLASMA PROTEOMIC SAMPLE (Day 1 visit): A blood sample for plasma proteomic 
analysis will be taken at each timepoint according to Section 7.2.4. 
OPTIONAL TRANSCRIPTOMIC SAMPLES (Day 1 and Day 14 visits): Two blood 
samples for possible whole blood transcriptomic analysis will be taken at each timepoint 
according to Section 7.2.11. 
7.1.3 Early termination
The following procedures will take place at the early termination visit in case of subject 
discontinuation/withdrawal: 
PHYSICAL EXAMINATION: A full physical examination will be performed according 
to Section 7.2.10 and any new revealed clinically significant abnormality since the last 
visit will be recorded as an AE.
ADVERSE EVENTS RECORDING: Any new AE/SAE occurred since the last visit will 
be checked and recorded in the eCRF. The status of ongoing AEs will be checked and 
updated in the eCRF when applicable. Moreover, in case of any new clinically significant 
abnormality revealed during the examination or procedures, it will be recorded as an AE. 
CONCOMITANT MEDICATIONS CHECK: Concomitant medications taken by the 
subject since the last visit will be checked and recorded in the eCRF.


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 39/73
BLOOD TESTING: Blood sample collection for safety evaluations (clinical chemistry, 
haematology, fasting glucose) and immunogenicity according to Sections 7.2.2.1 and 
7.2.2.4. 
VITAL SIGNS: Measurement of systolic and diastolic blood pressure, pulse rate, 
respiratory rate, and body temperature according to Section 7.2.8.
LOCAL ECG: Single 12-lead ECG will be used to measure heart rate, PR, QRS, and 
QTcF according to Section 7.2.9.
PULMONARY ASSESSMENTS: Oxygen saturation, Spirometry (FEV1, FEV1 % of 
predicted normal and lower limit of normal value, FVC, FVC % of predicted normal and 
lower limit of normal value, and FEV1/FVC), and diffusing capacity (DLCO [unadjusted], 
DLCO % predicted, DLCO corrected for haemoglobin, DLCO corrected for haemoglobin % 
predicted, KCO, and VA) will be measured according to Section 7.2.7.
7.1.4 Study restrictions and standardisation
The following restrictions must be applied and re-checked as appropriate at each visit:
No smoking cigarettes (or e-cigarettes) or nicotine- or tobacco-containing products during 
the treatment period
No strenuous exercise within 24 hours prior to and during each visit
No caffeine-containing foods and beverages within 10 hours prior to and during each visit
No intake of beverages or food containing alcohol within 48 hours prior to and during 
each visit
No intake of food for at least 10 hours prior to collection of clinical chemistry and fasting 
glucose.
If these restrictions are not respected, the visit can be rescheduled once and all the information 
regarding restriction(s) not respected, will be recorded in the eCRF. If the restrictions are again 
not respected, the visit will be performed anyway and all the information regarding restriction 
not respected will be recorded in the eCRF.
7.2 Investigations
In case of coinciding investigations, the timepoint for blood collection for PK evaluation takes 
priority over any other scheduled study activities, e.g., vital signs and oxygen saturation. Where 
other activities are scheduled together with the PK blood collection, these will be performed in 
a sequence allowing for blood sampling exactly at the scheduled timepoint. The exact time of 
each activity will be recorded in the eCRF.
Due to the variability in sampling requirements at different laboratories, the total volume of 
blood collected from each subject may vary. The approximately blood volume to be withdrawn 
per subject will be around 250 mL.


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 40/73
7.2.1 Blood collection for pharmacokinetic evaluation
7.2.1.1 Sample collection for PK evaluation and sample preparation
The laboratory analysis will be carried out following GCP.
The analytical procedures will be described in a separate analytical protocol. Validation data 
and details of the analytical procedures will be gathered in an analytical report that will be 
included in the Clinical Study Report.
7.2.1.2 Determination of CHF10067
Blood samples (1 sample = 3.5 mL) for determination of serum CHF10067 will be collected at 
the following timepoints: pre-dose (within 75 minutes from start of infusion), at the end of 
infusion, 2, 4, 8, and 20 hours after the end of infusion and 5, 7, 14, 28, 56, and 84 days 
post-dose. The selected timepoints are based on the results obtained after single dose in healthy 
subjects. Timepoints may be adjusted during the study if the PK profile in IPF patients is 
significantly different than healthy subjects. In that case, decisions will be taken by the Safety 
Advisory Committee and appropriately documented. The total number of timepoints is not 
expected to be modified. 
The time deviation window for PK sampling will be:
± 5 minutes for timepoints ≤ 2 hours
± 15 minutes for timepoints > 2 hours and ≤ 8 hours
± 1 hour for the timepoint of 20 hours
± 1 day for Days 5 and 7
± 2 days for Days 14, 28, 56, and 84. 
The processing, storage and shipment of samples are detailed in the Laboratory Manual 
document.
7.2.2 Blood collection for safety evaluation
Blood collection and sample preparation will be performed according to procedures provided 
by the local laboratory and central laboratories (where relevant) which will be in charge to 
transmit the results and the laboratory normal ranges for entry in the eCRF.
7.2.2.1 Clinical laboratory evaluations
The following blood samples will be collected at each visit:
Blood for serum clinical chemistry testing (creatinine, urea, aspartate aminotransferase, 
alanine aminotransferase, gamma-glutamyl transpeptidase, total bilirubin, alkaline 
phosphatase, sodium, potassium, and chlorine), and fasting glucose


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 41/73
Blood for haematology testing (red blood cells count, white blood cells count and 
differential (neutrophils, eosinophils, lymphocytes, monocytes, basophils; % and values), 
total haemoglobin, haematocrit, and platelets count).
For exclusion criteria no. 24, in case clinically relevant abnormal laboratory values are observed 
at screening that suggest a temporary condition and requiring further clinical investigation, the 
subject will be asked to return to clinic for a maximum of twice before treatment, to perform 
again the testing measurement. If at that time no abnormalities are observed, the subject can be 
included in the study, otherwise the subject will be discharged and recorded as screening failure.
The volume of blood required for these samples may vary between sites. 
7.2.2.2 Serology
The following blood sample will be collected at screening:
Blood for serum serology testing (HIV1, HIV2, Hepatitis B, and Hepatitis C).
The volume of blood required for this sample may vary between sites. 
7.2.2.3 Pregnancy and follicle-stimulating hormone testing 
The following blood samples will be collected at screening:
Blood for pregnancy testing (females of childbearing potential)
Blood for follicle-stimulating hormone testing (post-menopausal subjects only).
The volume of blood required for these samples may vary between sites. 
7.2.2.4 Immunogenicity
The following blood samples will be collected pre-dose and Days 14, 28, 56, and 84:
5 mL of blood for immunogenicity assessments (serum non-isotype ADAs) and nAb (in 
case of ADA positive result). 
The analytical procedures will be described in a separate analytical protocol. Validation data 
and details of the analytical procedures will be gathered in an analytical report that will be 
included in the Clinical Study Report. The processing, storage and shipment of samples are 
detailed in the Laboratory Manual document.
Antibodies to CHF10067 will be evaluated in blood samples collected from all subjects 
according to the study schedule (Section 7.1). Additionally, samples should be collected at the 
early termination visit from subjects who discontinued study drug or were withdrawn from the 
study. These samples will be tested by the Sponsor or Sponsor's designee. 


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 42/73
Samples will be screened for antibodies binding to CHF10067, and the titer of confirmed 
positive samples will be reported. Other analyses may be performed to further characterise the 
immunogenicity of CHF10067. In particular, positive ADA samples will be also evaluated for 
the presence of IgE CHF10067, to clarify the relationships between this ADA subtype and the 
presence of adverse reactions. 
The detection and characterisation of antibodies to CHF10067 will be performed using a 
validated assay method by or under the supervision of the Sponsor. All samples collected for 
detection of antibodies to study drug will also be evaluated for CHF10067 concentration, to 
enable interpretation of the antibody data. Antibodies may be further characterised and/or 
evaluated for their ability to neutralise the activity of the study drug. Samples may be stored for 
a maximum of 20 years (or according to local regulations) following the last subject’s final visit 
for the study at a facility selected by the Sponsor to enable further analysis of immune responses 
to CHF10067. 
7.2.2.5 Systemic markers of immediate hypersensitivity reactions
Subjects will be monitored up to 8 hours post-dose for immediate hypersensitivity reactions 
and will be discharged if no symptoms are reported. If a subject experiences symptoms of an 
immediate hypersensitivity reactions, they may remain at the clinical site overnight until the 
resolution of symptoms. Refer to Section 7.2.2.5.1 for recording of immediate hypersensitivity 
reactions.
The following blood samples will be collected for analysis of systemic markers* of immediate 
hypersensitivity reactions pre-dose (all subjects) and post-dose (1 and 2 hours after the start of 
reaction only if required). 
-
Serum markers of cytokine release syndrome (interferon-γ [IFN-γ], tumour necrosis 
factor-α [TNF-α], interleukin [IL]-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 [p70], and 
IL-13)
-
Serum mast cell tryptase
-
Complement markers (plasma C3a, plasma C5a, serum CH50, and plasma SC5b-9)
-
Serum CHF10067 IgE 
*During the study, the markers analysed may be adjusted as required; therefore, due to the 
potential variability in blood volume, this has not been specified. Any adjustment will be with 
consideration for subject safety and operational activities. 
7.2.2.5.1 Management and documenting of immediate hypersensitivity reactions
Immediate hypersensitivity reactions are known and anticipated reactions occurring with 
monoclonal antibodies. Standard precautions must be taken for the subjects regarding routine 
IV infusion complications. Appropriate medical management according to local guidelines and 
standard operating procedures should be implemented if an immediate hypersensitivity reaction 
is suspected (e.g., appropriate medical treatment, reducing or stopping the infusion rate, etc.).


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 43/73
Immediate hypersensitivity reactions [15] should be considered in all cases where any 
symptoms or signs related to the acute/hypersensitivity reactions occur during or within 24 
hours from infusion. All efforts should be made to accurately document symptoms, signs, and 
vital signs to allow accurate characterisation of the reaction. 
In case of occurrence of symptoms and signs indicative of the immediate hypersensitivity 
reactions the Investigator is asked to duly record (but not limited to) the following data: 
Exact time when the reaction started and the duration of the reaction
Oxygen saturation, respiratory rate, blood pressure, and 12-lead ECG 
Signs or symptoms including, but not limited to:
-
cutaneous and SC involvement: generalised erythema, urticaria, periorbital oedema, 
angioedema, pruritis, or flushing 
-
signs of cardiovascular compromise: cyanosis, arrhythmia, collapse, diaphoresis, or 
incontinence
-
nervous system involvement: dizziness, confusion, or loss of consciousness
-
gastrointestinal tract involvement: abdominal pain, vomiting, or nausea
-
respiratory involvement: dyspnoea, wheezing-bronchospasm, stridor, chest, or throat 
tightness.
If any other symptoms/signs, these should be specified. In addition, additional blood samples 
will be collected as described in Section 7.2.2.5. 
The severity grade of the immediate hypersensitivity reactions should be assessed by the 
Investigator, considering the following grading system [18]:
1. Mild (skin and SC tissues only)
a.
Generalised erythema, urticaria, periorbital oedema, or angioedema.
2. Moderate (features suggesting respiratory, cardiovascular, or gastrointestinal tract 
involvement)
a.
Dyspnoea, stridor, wheeze, bronchospasm, chest, or throat tightness
b. Abdominal pain, nausea, or vomiting
c.
Dizziness (presyncope), or diaphoresis.
3. Severe (hypoxia, hypotension, or neurological compromise)
a.
Cyanosis or hypoxemia (oxygen saturation ≤ 92%)
b. Hypotension (systolic blood pressure < 90 mmHg)
c.
Confusion, collapse, loss of consciousness, or incontinence.


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 44/73
Characterisation of the immediate hypersensitivity reactions will be performed at the end of 
study after all clinical and biochemical data are available and analysed by Safety Advisory 
Committee. 
Anaphylactic reactions, defined as IgE mediated, are not expected to occur during the first 
administration. However, when an anaphylactic reaction is suspected, CHF10067 should be 
discontinued immediately and appropriate therapy as per standard of care including 
epinephrine, diphenhydramine, corticosteroids, oxygen, and volume expansion should be 
administered. 
Clinical criteria to diagnose anaphylaxis are summarised below [19]: 
Anaphylaxis is highly likely when any 1 of the following 3 criteria is fulfilled: 
1. Acute onset of illness (minutes to several hours) with involvement of the skin, 
mucosal tissue, or both (e.g., generalised urticaria, pruritis, flushing, or angioedema)
AND at least 1 of the following
a.
Respiratory compromise (e.g., Dyspnoea, wheeze-bronchospasm, 
stridor, chest tightness, or hypoxemia [oxygen saturation ≤ 92%])
b. Hypotension (blood pressure < 90 mmHg) or associated symptoms of 
end-organ dysfunction (e.g., collapse, syncope, or incontinence).
2. Two or more of the following that occur after exposure (minutes to several hours): 
a.
Involvement of the skin, mucosal tissue, or both (e.g., generalised urticaria, 
pruritis, flushing, or angioedema)
b. Respiratory compromise (e.g., dyspnoea, wheeze-bronchospasm, stridor, 
chest tightness, or hypoxemia [oxygen saturation ≤ 92%])
c.
Hypotension (blood pressure < 90 mmHg) or drop in blood pressure (> 30% 
of subject’s baseline) or associated symptoms of end-organ dysfunction (e.g., 
collapse, syncope, or incontinence)
d. Persistent gastrointestinal symptoms (e.g., abdominal pain, nausea, or 
vomiting).
3. Reduced blood pressure after exposure to a known allergen for that subject (minutes to 
several hours): 
a.
Systolic blood pressure of < 90mmHg 
OR 
b. Drop in systolic blood pressure > 30% decrease from that subject’s baseline.


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 45/73
Additional precautions should be taken for the next subjects to be treated, such as intake of 
pre-treatment medication or changes in the infusion rate and duration and will be discussed at 
Safety Advisory Committee level and communicated to all the enrolling sites before the next 
dosing. 
7.2.3 Blood collection for transglutaminase 2 evaluation
The following blood samples will be collected pre-dose and on Days 14, 28, 56, and 84:
4 mL of blood for plasma TG2 levels.
Evaluation of TG2 will also include a group of 24 samples obtained from healthy subjects (i.e., 
from a biobank), in order to allow for a comparison of TG2 levels between healthy volunteers 
and IPF patients. The analytical procedures will be described in a separate analytical protocol. 
Validation data and details of the analytical procedures will be gathered in an analytical report 
that will be included in the Clinical Study Report. The processing, storage, and shipment of 
samples are detailed in the Laboratory Manual document.
7.2.4 Blood collection for proteomic analysis
The following blood samples will be collected:
8.5 mL of blood for serum proteomic analysis (pre-dose on Day 1 and on Day 14).
6 mL of blood for plasma proteomic analysis (pre-dose on Day 1). 
The processing, storage and shipment of samples are detailed in the Laboratory Manual 
document. The samples for proteomic analysis will be collected for exploratory purposes and 
will be retained until up to 20 years to be possibly used for post-hoc analysis and investigations. 
Results will not be part of the current statistical analysis and will not be included in the Clinical 
Study Report.
7.2.5 Mucosal sample collection by naso-absorption
Two mucosal samples (1 from each nostril) will be collected pre-dose on Day 1 and on Day 14 
via naso-absorption. Naso-absorption is a non-invasive procedure using a synthetic absorptive 
matrix swab to absorb mucosal lining fluid from the mucosa within the nose. A detailed 
description of the naso-absorption procedure will be outlined in separate documents.
The processing, storage, and shipment of samples are detailed in the laboratory manual 
document. The mucosal samples will be collected for exploratory purposes and will be retained 
until up to 20 years to be possibly used for post-hoc analysis and investigations. Results will 
not be part of the current statistical analysis and will not be included in the Clinical Study 
Report. 
7.2.6 Urine collection for safety evaluation
The following urine sample will be collected at screening:


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 46/73
Urine sample for urinalysis – quantitative (proteins) and urinalysis – qualitative (ketones, 
microscopic examination of the sediment)
Urine sample for drug test (cannabinoids, opiates, cocaine, benzodiazepines, 
amphetamines, barbiturates)
Urine sample for cotinine test.
The following urine samples will be collected on the Day 1, 28, 56, and 84 visit:
Urine sample for pregnancy test.
Urine collection and sample preparation will be performed according to procedures provided 
by the local laboratory which will be in charge to transmit the results to the Investigator for 
entry in the eCRF.
7.2.7 Pulmonary assessments for safety evaluation
7.2.7.1 Spirometry 
Spirometry will be assessed at the following timepoints: screening, 7, 28, 56, and 84 days post-
dose and in case of early termination visit.
Spirometry will be assessed centrally. The specific procedures for centralized spirometry will 
be provided to the Investigator by the centralized spirometry company. The same brand and 
model of spirometer will be provided by the centralised spirometry company for all 
measurements and adjusted for the ATS/ERS standards [20]. Lung function measurements will 
be done with subjects sitting with the nose clipped after at least 10 minutes rest. Values will be 
corrected for body temperature and pressure (saturated) conditions. 
The following parameters (but not limited to) will be recorded: FEV1, FVC, FEV1% of 
predicted normal and lower limit of normal value, FVC % of predicted normal and lower limit 
of normal value, and FEV1/FVC ratio. 
Predicted values of FEV1 will be calculated according to formulas reported by Quanjer et al. 
[21]. 
For FEV1 and FVC, the highest value from 3 technically satisfactory attempts will be recorded 
in the eCRF (irrespective of the curve they come from). The chosen value should not exceed 
the next one by more than 150 mL. If the difference is larger, up to 8 measurements will be 
made and the largest value be reported. In order to be considered as technically satisfactory 
attempts, measurements should be free from cough and false-start and meet all the ERS/ATS 
criteria. The FEV1/FVC should be taken from the highest FEV1 and FVC values (even if not 
coming from the same curve). The acceptability criteria for spirometry assessment will be 
further specified in separate documents. 
For inclusion criterion no. 8 if the criterion is not met at screening, the subject may repeat the 
tests. If at that time the values fall within the ranges specified, the subject can be included in 
the study, otherwise the subject will be discharged and recorded as screening failure. 


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 47/73
7.2.7.2 Diffusing capacity 
Diffusing capacity will be assessed at the following timepoints: screening, 28, 56, and 84 days 
post-dose and in case of early termination visit. 
Diffusing capacity will be assessed locally using the device available at each site. The devices 
used should be in accordance with current requirements issued by ERS/ATS in 2017 [22]. The 
test will be performed with subjects in a sitting position and nose clipped. Subjects should avoid 
exercise and cigarette smoking on the day of the test. All the results will be uploaded to a central 
database and will be evaluated centrally. 
The following parameters (but not limited to) will be reported: DLCO (unadjusted), DLCO % 
predicted, DLCO corrected for haemoglobin, DLCO corrected for haemoglobin % predicted, KCO, 
and VA.
The reported DLCO will be corrected for the current haemoglobin level, using reference 
equations.
For inclusion criterion no.9, if the criterion is not met at screening, the subject will repeat the 
test. If at that time the values fall within the ranges specified, the subject can be included in the 
study; otherwise, the subject will be discharged and recorded as screening failure.
7.2.7.3 Oxygen saturation
Oxygen saturation will be measured by continuous pulse oximetry at screening and from pre-
dose to 10 hours post-dose at the following timepoints: pre-dose, every 15 minutes during the 
infusion (e.g., 15, 30, 45, 60, 75, 90, 105, etc.), at the end of infusion and 30 min, 1, 2, 3, 4, 6, 
8 hours after the end of the infusion. Oxygen saturation will also be measured at 20 hours after 
the end of the infusion, and 5, 7, 14, 28, 56, and 84 days post-dose and in case of early 
termination visit.
For inclusion criterion no.7, if the criterion is not met at screening or at the Day 1 visit, the 
subject will repeat the test. If at that time the values fall within the ranges specified, the subject 
can be included in the study, otherwise the subject will be discharged and recorded as screening 
failure.
7.2.8 Vital signs
Vital signs (systolic and diastolic blood pressure, pulse rate, respiratory rate, and body 
temperature) will be evaluated at the following timepoints: screening, pre-dose, every 15 
minutes during the infusion (e.g., 15, 30, 45, 60, 75, 90, 105, etc.), at the end of infusion and 
30 min, 1, 2, 3, 4, 6, 8 and 20 hours after the end of the infusion and 5, 7, 14, 28, 56, and 84 
days post-dose and in case of early termination visit.
Blood pressure will be measured in duplicate, after 5 minutes in the supine position. The single 
values and the average of duplicate blood pressure measurements will be reported in eCRF, and 
the average will be used to assess the subject’s eligibility. 


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 48/73
7.2.9 Local 12-lead electrocardiogram
A triplicate 12-lead ECG will be performed to assess eligibility and a single 12-lead ECG will 
be evaluated at pre-dose on Day 1, and Days 2, 7, 28, and 84 days post-dose and in case of early 
termination visit. 
The following parameters will be recorded: heart rate, PR, QRS, and QTcF.
7.2.10 Physical examination
A comprehensive full physical examination or abbreviated symptom-directed physical 
examination will be performed at each visit. Any new revealed clinically significant 
abnormality since the last visit will be recorded as an AE. 
7.2.11 Optional blood collection for transcriptomic analysis
The following blood samples will be collected pre-dose on Day 1 and on Day 14:
2 × 2.5 mL of blood for whole blood transcriptomic analysis.
The processing, storage and shipment of samples are detailed in the Laboratory Manual 
document. The samples for transcriptomic analysis will be collected for exploratory purposes 
and will be retained until up to 20 years to be possibly used for post-hoc analysis and 
investigations. Results will not be part of the current statistical analysis and will not be included 
in the Clinical Study Report. Sample collection and analysis will only be conducted in subjects 
who have provided a separate and specific informed consent.
8.
PHARMACOKINETIC AND OTHER ASSESSMENTS
8.1 Pharmacokinetic Assessments
The following PK parameters will be calculated, whenever possible, for each subject based on 
the serum concentrations of CHF10067 following a single IV administration: 
Area under the concentration-time curve (AUC) from 0 to the last quantifiable 
concentration (AUC0-t)
AUC extrapolated to infinity (AUCinf)
Maximum observed concentration (Cmax)
Time to Cmax (tmax)
Concentration at steady state of infusion (Cinf)
Clearance (CL)
Volume of distribution (Vz)
Terminal half-life (t1/2).


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 49/73
The PK analysis will be performed using WinNonlin Phoenix 6.2 or later (Pharsight 
Corporation, Palo Alto, CA, USA). Actual elapsed time from dosing will be used to estimate 
all individual PK parameters. Standard non-compartmental methods will be used for the 
calculation of the following parameters from the individual serum drug concentrations versus 
time profile. 
8.2 Other Assessments
Levels of TG2 in plasma will be collected for exploratory assessment. 
9.
SAFETY ASSESSMENTS
9.1 Safety Variables
Safety and tolerability will be assessed through the monitoring of the following: 
AEs and adverse drug reactions (ADRs)
Vital signs (systolic and diastolic blood pressure, pulse rate, respiratory rate, and body 
temperature)
Oxygen saturation measured via pulse oximetry
12-lead ECGs (heart rate, PR, QRS, and QTcF)
Clinical laboratory evaluations: clinical chemistry (including fasting glucose) and 
haematology
Physical examinations
Spirometry (FEV1, FVC, FEV1 % of predicted normal and lower limit of normal value, 
FVC % of predicted normal and lower limit of normal value, and FEV1/FVC ratio)
Diffusing capacity (DLCO [unadjusted], DLCO % predicted, DLCO corrected for 
haemoglobin, DLCO corrected for haemoglobin % predicted, KCO, and VA)
ADAs and nAb
Analysis of systemic markers* of immediate hypersensitivity reactions pre-dose and post-
dose (post-dose only if required) including: 
-
markers of cytokine release syndrome (IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-
10, IL-12 (p70), and IL-13)
-
mast cell tryptase
-
complement markers (C3a, C5a, CH50, and SC5b-9)
-
CHF10067 IgE.
*During the study, the markers analysed may be adjusted as required. Any adjustment will be 
with consideration for subject safety and operational activities. 


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 50/73
9.2 Emergency Situation
In case of health emergency, including COVID-19, the Investigator/site staff must take all 
necessary precautions to minimise and avoid the risk of transmission and exposure to study 
subjects and site staff, according to local guidelines. In that particular case: 
a time window for study visits could be allowed when subjects are not able to arrive to 
the site or to attend the visit
onsite study visits could be cancelled or replaced by phone calls, or some assessments 
could be missed. 
Special case of COVID-19 outbreak:
Every effort should be made by the site to confirm all suspected incidences of COVID-19 in 
accordance with local diagnostic guidelines. Documentation of testing and results obtained 
outside the clinical site, should be collected within 14 days of confirmed diagnosis (or whenever 
possible) and recorded in the eCRF. 
All incidences of COVID-19 as well as the impact on study visits and subject completion must 
be captured in the eCRF.
Occurrence of SARS-CoV-2 infection and/or COVID-19 disease during the study does not 
automatically lead to withdrawal of the subject. It will be up to the Investigator’s judgement to 
withdraw the subject from the study if he/she deems that remaining in the study will place the 
subject and/or the clinical site at undue risk by continuing their participation. All efforts should 
be made to keep the subject on study drug, if possible. 
In case study visits or procedures are modified or missed due to COVID-19, the relevant 
information will be recorded in the eCRF. 
As of the date of this protocol version, there is no specific treatment for COVID-19 and several 
vaccine therapies have been developed and approved by health authorities with vaccination 
campaigning being initiated worldwide. For all confirmed cases of COVID-19/SARS-CoV-2 
the Investigator must follow the standard of care in accordance with local treatment guidelines. 
All concomitant treatments must be recorded in the eCRF. 
In case of COVID-19 suspect, Investigators are encouraged to perform diagnostic testing 
locally or obtain results of tests from hospital where the event was diagnosed and/or managed, 
and every effort should be made to complete the assessments required by the current local 
guidelines for COVID-19 management (e.g., SARS-CoV-2 test, chest imaging) and to 
guarantee the appropriate management.


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 51/73
10.
ADVERSE EVENT REPORTING
10.1 Definitions
An Adverse Event is “any untoward medical occurrence in a patient or clinical study subject 
administered a medicinal product and which does not necessarily have a causal relationship 
with this treatment”.
An AE can therefore be any unfavourable and unintended sign (including abnormal laboratory 
finding), symptom, or disease temporally associated with the use of a medicinal product, 
whether or not considered related to the medicinal product.
An Adverse Drug Reaction is an “untoward and unintended responses to an investigational 
medicinal product related to any dose administered”.
All AEs judged by either the reporting Investigator or the Sponsor as having a reasonable causal 
relationship to a medicinal product qualify as adverse reactions. The expression “reasonable 
causal relationship” means to convey in general that there are facts (evidence) or arguments 
meant to suggest a causal relationship.
The definition covers also medication errors and uses outside what is foreseen in the protocol, 
including misuse and abuse of the product.
A Serious Adverse Event (SAE)/Serious Adverse Drug Reaction is any untoward medical 
occurrence or effect that at any dose falls in one or more of the following categories:
Results in death
Death is not an AE but an outcome. It is the cause of death that should be regarded as the AE. 
The only exception to this rule is “sudden death” where no cause has been established; in this 
latter instance, “sudden death” should be regarded as the AE and “fatal” as its reason for being 
serious.
Is life-threatening
Life-threatening refers to an event in which the subject was at risk of death at the time of the 
event (e.g., aplastic anaemia, acute renal failure, and anaphylaxis). The term does not refer to 
an event which hypothetically might have caused death if it were more severe.
Requires hospitalisation or prolongation of existing hospitalisation
Hospitalisation refers to a situation whereby an AE is associated with unplanned formal 
overnight admission into hospital, usually for purpose of investigating and/or treating the AE. 
Hospitalisation for the treatment of a medical condition that occurs on an “elective” or 
“scheduled” basis or for a pre-existing condition that did not worsen during the study should 
not necessarily be regarded as an AE. Complications that occur during the hospitalisation are 
AEs. If a complication prolongs hospitalisation, the event is an SAE. Emergency room visits 


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 52/73
that do not result in a formal admission into hospital should be evaluated for one of the other 
seriousness criteria (e.g., life-threatening; persistent or significant disability or incapacity; 
medically significant).
Results in persistent or significant disability or incapacity
The term significant disability should be viewed as any situation whereby an AE has a clinically 
important effect on the subject’s physical or psychological well-being to the extent that the 
subject is unable to function normally.
Is a congenital anomaly or birth defect
Is a medically significant adverse event
This criterion allows for any situations in which important AE/adverse reactions that are not 
immediately life-threatening or do not result in death or hospitalisation may jeopardise the 
subject’s health or may require intervention to prevent one of the above outcomes.
Examples of such events are: intensive treatment in an emergency room or at home for allergic 
bronchospasm; blood dyscrasias or convulsions that do not result in hospitalisation; or 
development of drug dependency or drug abuse.
Medical and scientific judgment should be exercised in deciding whether an event is serious 
because medically significant.
Any suspected transmission via a medicinal product of an infectious agent is also considered a 
serious adverse reaction.
A Non-Serious Adverse Event/Non-Serious Adverse Drug Reaction is an AE or ADR that 
does not meet the criteria listed above for an SAE/serious adverse drug reaction.
10.2 Expectedness
An expected adverse reaction is an adverse reaction, the nature or severity of which is consistent 
with the applicable reference safety information (included in the IB for CHF10067) otherwise 
it is considered unexpected.
Reports which add significant information on specificity or severity of a known, already 
documented serious ADR constitute unexpected events. For example, an event more specific 
or more severe than described in the reference safety information would be considered as 
“unexpected”. Examples of such events are: (a) acute renal failure as a labelled ADR with a 
subsequent new report of interstitial nephritis and (b) hepatitis with a first report of fulminant 
hepatitis.
In the event an exacerbation is interpreted as due to lack of efficacy, it should not be classified 
as drug related.


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 53/73
10.3 Intensity of Adverse Event
For the classification of AEs severity (except for immediate hypersensitivity reactions severity, 
see below), the Common Terminology Criteria for Adverse Events (CTCAE) [23] will be used:

Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated. 

Grade 2 Moderate; minimal, local, or noninvasive intervention indicated; limiting age-
appropriate instrumental Activities of Daily Living (ADL)*. 

Grade 3 Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting 
self-care Activities of Daily Living**. 

Grade 4 Life-threatening consequences; urgent intervention indicated. 

Grade 5 Death related to AE. 
*Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the 
telephone, managing money, etc. 
**Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking 
medications, and not bedridden.
In order to guarantee objectivity and consistency in the evaluation of AEs (including 
classification of severity), the proposed guidance should be followed in alignment with best 
medical practice.
Laboratory abnormalities and other clinical assessments (e.g., 12-lead ECG) will be reported 
as AEs if judged by the Investigator as being clinically significant.
In case of laboratory evaluations or other clinical assessments (e.g., 12 -lead ECG) not listed in 
the CTCAE grading table, the AE severity will be judged by the Investigator based on the local 
ranges.
Taking into consideration the disease examined in the current study, it should be acknowledged 
that the guidance may not always be applied. Therefore, although the guidance should be 
followed, whenever possible, in order to ensure an accurate and objective evaluation of the AEs, 
the final decision on the severity classification remains the responsibility of the Investigator. 
For the specific classification of severity and management of immediate hypersensitivity 
reactions, refer to Section 7.2.2.5.1.


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 54/73
10.4 Causality Assessment
The following “binary” decision choice will be used by the Investigator to describe the causality 
assessment:
Reasonable possibility of a relatedness
No reasonable possibility of relatedness.
The expression “reasonable possibility of relatedness” is meant to convey, in general, that there 
are facts (evidence), or arguments meant to suggest a causal relationship.
The Investigator will be asked to consider the following before reaching a decision on causality 
assessment:
Time relationship between study drug intake and event’s onset
Dechallenge (did the event abate after stopping drug?)
Rechallenge (did the event reappear after reintroduction?)
Medical history
Study treatment(s)
Mechanism of action of the study drug
Class effects
Other treatments-concomitant or previous
Withdrawal of study treatment
Lack of efficacy/worsening of existing condition
Erroneous treatment with study medication (or concomitant)
Protocol related process.
10.5 Action Taken with the Study Drug due to an Adverse Event
Dose not changed
Drug permanently withdrawn
Drug temporarily interrupted
Dose reduced
Dose rate reduced
Not applicable.
10.6 Other Actions Taken
Specific therapy/medication
Concomitant procedure.


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 55/73
10.7 Outcome
Each AE must be rated by choosing among:
Recovered/resolved
Recovering/resolving
Not recovered/not resolved
Recovered with sequelae/resolved with sequelae
Fatal
Unknown.
10.8 Recording Adverse Events
All AEs occurring during the course of the study must be documented in the AE page of the 
eCRF. Moreover, if the AE is serious, the SAE Form must also be completed. 
It is responsibility of the Investigator to collect all AEs (both serious and non-serious) derived 
by spontaneous, unsolicited reports of subjects, by observation, and by routine open 
questionings.
The recording period for AEs is the period starting from the informed consent signature until 
the subject’s study participation ends.
Clinically significant abnormalities detected at screening visit not due to a pre-existing 
condition or clinically significant changes at the following visits in the medical opinion of the 
Investigator must be reported as AEs in the eCRF.
If a clinically significant abnormal laboratory finding or other abnormal assessment meets the 
definition of an AE, then the AE eCRF page must be completed, as appropriate. A diagnosis, if 
known, or clinical signs and symptoms if diagnosis is unknown, rather than the clinically 
significant abnormal laboratory finding, should be reported on AE eCRF page. If no diagnosis 
is known and clinical signs and symptoms are not present, then the abnormal finding should be 
recorded.
For pharmacovigilance purposes, all SAEs should be followed-up in order to elucidate as 
completely and practically as possible their nature and/or causality until resolution of all 
queries, clinical recovery is complete, laboratory results have returned to normal, stable 
condition is reached or until the subject is lost to follow-up. Follow-up may therefore continue 
after the subject has left the study. In this case, the follow-up will continue with no timelines 
for related SAEs, while for unrelated SAEs the type and extent of follow-up undertaken will be 
determined for each individual case and will depend upon the nature (e.g., events with poor 
prognosis or which do not resolve), severity, and medical significance of the event. 


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 56/73
10.9 Reporting Serious Adverse Events to Chiesi
The Investigator must report all SAEs to the Fortrea Safety Contact listed below within 24 hours 
of awareness. The information must be sent by providing the completed paper SAE form. At a 
later date, the Fortrea Safety Contact will report all information to Chiesi Global 
Pharmacovigilance, the Clinical Project Manager, and the Clinical Research Physician.
Safety Contact
Fax No.
E-mail
Fortrea Safety Contact
+1 609 419 2609
SAEIntake@fortrea.com
Chiesi Safety Contact
+39 0521 1885003
CT_CDS@chiesi.com 
Reporting of SAEs from the Investigator site is from the time of subject’s signature of 
informed consent and until the subject’s study participation ends. After this date, even if 
no active monitoring of subjects is required, SAEs occurring to a subject should be 
reported if the Investigator becomes aware of them.
Up to the closure of the site, SAE reports should be reported to the Fortrea Safety Contact. 
New SAEs occurring after the site is closed should be reported directly to the Chiesi 
Safety Contact.
10.10 Reporting Serious Adverse Events to Regulatory Authorities/Ethics Committee
All SUSARs, which occur with the investigational medicinal products within or outside the 
concerned clinical study, if required, will be reported in compliance with the timelines and 
standards for reporting SUSARs. The Medicines and Healthcare products Regulatory Agency 
(MHRA) will be informed through MHRA Individual Case Safety Report (ICSR) Submission 
portal, while other relevant Regulatory Authorities in accordance with local requirements.  The 
ECs and the Investigators will be informed by Council for International Organisations of 
Medical Sciences I form or by periodic line listings produced by Chiesi Global 
Pharmacovigilance.
With regard to regulations in force for Pharmacovigilance, the Investigators must fulfil their 
obligation according to the law in force in their countries.
10.11 General Notes
In case of death, a comprehensive narrative report of the case should be prepared by the 
Investigator and sent to the Fortrea Safety Contact together with the SAE form, retaining 
a copy on site.
If an autopsy is performed, copy of autopsy report should be actively sought by the 
Investigator and sent to the Fortrea Safety Contact as soon as available, retaining a copy 
on site.


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 57/73
All documents provided by the Investigator or site staff to the Fortrea Safety Contact must 
be carefully checked for respect of confidentiality. All personal subject’s data must be 
redacted.
In case of pregnancy discovered after treatment with study drug, the subject may remain 
on the study until completion for safety monitoring purposes, if these are considered safe 
by the Investigator. The subject will be asked (with a separate consent) to be followed 
with due diligence until the outcome of the pregnancy is known and till the age of one 
year of the child to detect any congenital anomaly or birth defect. The pregnancy must be 
reported by the Investigator within 24 hours by fax/e-mail to the Fortrea Safety Contact 
using the paper Pregnancy Report Form. The Fortrea Safety Contact will inform Chiesi 
of the pregnancy within 1 working day of being notified. 
The first 2 pages of the Pregnancy Report Form should be completed by the Investigator 
with all the available information and sent to the Fortrea Safety Contact. Information 
collected in specific sections relative to the pregnancy will be recorded in the form only 
upon signature of the specific ICF by the subject/subject’s partner. The third page will be 
completed as soon as the Investigator has knowledge of the pregnancy outcome, together 
with a follow-up of the first 2 pages, if necessary (e.g., an update in the medications 
received during pregnancy by the mother). If it meets the criteria for immediate 
classification of a SAE (e.g., spontaneous or therapeutic abortion, stillbirth, neonatal 
death, congenital anomaly, birth defect) the Investigator should follow the procedure for 
reporting SAEs. 
If it is the partner, rather than the subject, who is found to be pregnant, the same procedure 
regarding pregnancy reporting is to be followed and the Pregnancy Report Form should 
be completed. 
If the pregnancy is discovered before taking any dose of study drug, the pregnancy does 
not need to be reported; it is only required that the subject is immediately withdrawn from 
the study.
Any ADR occurring with any marketed non-investigational medicinal product and/or 
concomitant medication during the study must be reported by the Investigator to his/her 
concerned Health Authority and/or to the relevant Marketing Authorisation Holders of 
the involved medicinal products according to the applicable laws. Additionally, also 
conditions of use outside the marketing authorisation of the medicinal products (i.e., 
off-label, overdose, misuse, abuse, and medication errors) or from occupational exposure, 
as well as cases of suspected drug interaction, pregnancy, breast-feeding exposure and 
lack of efficacy should be reported.
11.
DATA MANAGEMENT
An eCRF will be filled in by the Investigator and/or his/her representative designee.
Front-end edit checks will run at the time of data collection and back-end edit checks will be 
used by the Data Manager to check for discrepancies and to ensure consistency and 
completeness of the data.


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 58/73
Medical history, AEs, and concomitant procedures will be coded using the MedDRA 
dictionary; medications will be coded using the World Health Organisation Drug dictionary and 
Anatomical Therapeutic Chemical classification.
External data (PK, immunogenicity, immediate hypersensitivity reactions systemic markers, 
spirometry, diffusing capacity, plasma TG2 samples) will be processed centrally, sent to the 
designated Contract Research Organisation, and reconciled with the corresponding information 
recorded in the eCRF.
Access to electronic systems used for data collection will be granted to the study personnel only 
after appropriate training.
After the completion of data collection and cleaning, a review meeting will be held to determine 
the occurrence of any protocol violation and to define the subject populations for the analysis. 
Once the database has been declared to be complete and accurate, it will be locked, the 
randomisation codes will be opened, and the planned statistical analysis will be performed.
If the database is unlocked after the initial lock, the process must be carefully controlled and 
documented; updates to the study data must be authorised by Chiesi.
At the study conclusion, a complete copy of the study data will be created for archival purposes 
at Chiesi. The Investigators will receive copies of the subject data for retention at the 
investigational sites.
12.
STATISTICAL METHODS
12.1 Sample Size
This study is designed to explore the safety and tolerability of CHF10067 for the first time in 
subjects affected by IPF, while exposing a minimum number of subjects; therefore, no formal 
power calculation was performed. 
A sample size of 24 subjects (8 subjects per cohort; 6 treated with CHF10067 and 2 with 
placebo) is deemed adequate to assess safety and tolerability of CHF10067. In each cohort, a 
minimum of 2 subjects are required to be not receiving antifibrotic treatment (including subjects 
with previous use of antifibrotic treatment that has been stopped for at least 2 weeks prior to 
screening).
12.2 Analysis Sets
Safety set: all randomised subjects who receive a dose of study treatment, including partial 
dose.
PK set: all subjects from the safety population excluding subjects without any valid PK 
measurement or with important protocol deviations significantly affecting PK, for example, 
use of non-permitted medications. Exact definition of important protocol deviations 
significantly affecting PK will be discussed by the clinical team and described in a specific 


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 59/73
document before bioanalytical data are disclosed. Subjects will not be excluded on the basis 
of statistical analysis or for PK reasons, except in the cases defined in the European Medicine 
Agency guideline [24]. 
After unblinding, subjects will not be excluded on the basis of statistical or for PK reasons, 
except in the case of:
non-zero baseline concentration > 5% of Cmax
AUC0-t lower than 5% of the reference medicinal product geometric mean of AUC0-t 
(calculated without inclusion of data from the outlying subject)
below the limit of quantification concentration at all timepoints.
Pharmacokinetic variables will be analysed in the PK set. The safety set will be used in the 
analysis of all safety variables. In case of deviation between randomised treatment and 
treatment actually received, the treatment actually received will be used (i.e., an as-treated 
analysis will be performed).
12.3 Statistical Analysis
Detailed statistical analysis will be described in the Statistical Analysis Plan (SAP). The plan 
will be finalised before breaking the blind. 
12.3.1 Descriptive statistics 
Descriptive statistics for PK variables (except for tmax) will include n (number of observed 
values), arithmetic mean, standard deviation (SD), coefficient of variation (CV), geometric 
mean, geometric CV, median, minimum, and maximum. The variable tmax will be summarised 
by using n, median, minimum, and maximum.
All individual concentration data and PK variables will be listed. In addition, a listing of the 
actual sampling times relative to study treatment administration will be provided. 
Concentrations will be summarised by treatment and scheduled sampling time by using n, 
arithmetic mean, SD, CV, median, minimum, and maximum.
Descriptive statistics for the other continuous variables will include n, arithmetic mean, SD, 
median, minimum, and maximum.
For categorical variables, the number and percentage of subjects with a specific level of the 
variable will be presented. Missing values will not be used in percentage calculations.
12.3.2 Missing data
Further details on dealing with missing data, along with the handling of possible outliers, will 
be described in the SAP. Other critical missing data, if any, will be discussed during the review 
of the data. Decisions will be fully documented in the Data Review Report.


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 60/73
12.3.3 Subject demographics and baseline characteristics
The following variables will be summarised using descriptive statistics on the safety population 
(and on the PK population, if relevant): demographic characteristics (including age, sex, and 
race), height, weight, BMI, medical history and concomitant diseases, previous and 
concomitant medications, lung function, diffusing capacity, oxygen saturation, 12-lead ECG, 
vital signs, laboratories, and other safety parameters at screening and/or at baseline (pre-dose 
on Day 1).
12.3.4 Pharmacokinetic variables
CHF10067 serum AUC0-t, AUCinf, Cmax, tmax, Cinf, CL, Vz, and t1/2 will be summarised by dose 
level using descriptive statistics.
Serum concentration/time curves will be presented in linear/linear and log/linear scale. Plots 
will be presented by dose level, based on arithmetic means, and by subject, by showing the 
individual curves grouped by dose level (1 plot for each dose level) and ADA 
positivity/negativity (using different colours).
Dose proportionality in terms of CHF10067 AUC0-t, AUCinf, and Cmax will be evaluated using 
the power model, including the log-transformed PK parameters as dependent variables, and the 
log-transformed CHF10067 dose as a covariate. The slope for log-transformed dose will be 
estimated with its 90% confidence interval (CI) to examine dose proportionality.
12.3.5 Safety variables
All safety data will be listed. For all safety and immunogenicity variables, baseline is the last 
available assessment before the dose administration, which is either the screening assessment 
between Days -28 to -3 or the pre-dose assessment on Day 1.
12.3.5.1 Adverse events
The number of events and the number and percentage of subjects experiencing treatment 
emergent-adverse events (TEAEs), treatment-emergent ADRs, serious TEAEs, non-serious 
TEAEs, TEAEs by CTCAE grade, TEAEs leading to discontinuation of study drug and TEAEs 
leading to death will be presented by treatment. The aforementioned categories of AEs will be 
also summarised by System Organ Class and Preferred Term using the MedDRA dictionary.
12.3.5.2 Systemic markers for evaluation of immediate hypersensitivity reactions
Cytokine markers (IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 (p70), and IL-13), 
mast cell tryptase, complement markers (C3a, C5a, CH50, and SC5b-9), and CHF10067 IgE 
will be presented by subject for each post-dose timepoint as absolute value and change from 
baseline (if collected).


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 61/73
12.3.5.3 Immunogenicity 
Anti-drug antibody positive subjects will be defined as described in Section 7.2.2.4.
As a minimum, the following will be prepared: 
A table summarising for each ADA-positive subject:
-
dose administered
-
baseline ADA
-
maximal ADA timepoint
-
maximal ADA value
-
final ADA timepoint
-
final ADA value
-
pre-dose TG2 level
-
TG2 level at maximal ADA timepoint
-
CHF10067 AUCinf.
A table summarising for ADA-positive subject the ADA and nAb ranges by dose level.
12.3.5.4 Pulmonary assessments 
12.3.5.4.1 Spirometry 
The FEV1, FVC, FEV1/FVC, FEV1% of predicted and FVC% of predicted, will be summarised 
by dose level as absolute value, and absolute and relative change from baseline (i.e., the 
assessment at screening between Days -28 to -3) at each post-dose timepoint using descriptive 
statistics and 95% CIs. The frequency of subjects with FEV1% and FVC% below the lower 
limit of normal at each timepoint will be listed and summarised with descriptive statistics. 
Time profile plots by dose level will be presented for mean absolute and relative changes from 
baseline. 
12.3.5.4.2 Diffusing capacity
The DLCO unadjusted, DLCO % predicted, DLCO corrected for haemoglobin, and the other 
relevant variables collected will be summarised by dose level as absolute value and change 
from baseline (i.e., the assessment at screening between Days -28 to -3) at each post-dose 
timepoint using descriptive statistics and 95% CIs.
Time profile plots by dose level will be presented for DLCO corrected for haemoglobin and 
DLCO% predicted for mean changes from baseline. 
12.3.5.4.3 Oxygen saturation
The oxygen saturation will be summarised by dose level as absolute value and change from 
baseline (i.e., the pre-dose assessment on Day 1) at each post-dose timepoint using descriptive 


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 62/73
statistics and 95% CIs. Time profile plots by dose level will be presented for mean changes 
from baseline. 
12.3.5.5 ECG
At each post-dose timepoint, the following statistics will be presented by dose level for 12-lead 
ECG parameters (heart rate, PR, QRS, QTcF): 
mean absolute value with its 95% CI
mean change from baseline (i.e., the pre-dose assessment on Day 1) with its 90% CI
mean placebo-corrected change from baseline with its 90% CI.
Time profile plots, individual and by dose level, will be presented for change from baseline 
(i.e., the pre-dose assessment on Day 1). Time profile plots of mean difference versus placebo 
in change from baseline will be presented by dose level for heart rate and QTcF.
The number and percentage of subjects with the following will be presented by dose level at 
each post-dose timepoint and at any post-dose timepoint:
Males: QTcF > 450 ms, > 480 ms, and > 500 ms
Females: QTcF > 470 ms and > 500 ms
Both sexes: change from baseline in QTcF > 30 ms and > 60 ms.
12.3.5.6 Vital signs
At each post-dose timepoint the following statistics will be presented by dose level for systolic 
and diastolic blood pressure, pulse rate, respiratory rate, and body temperature: 
mean absolute value with its 95% CI
mean change from baseline (i.e., the pre-dose assessment on Day 1) with its 95% CI.
Time profile plots, individual and by dose level, will be presented for change from baseline 
(i.e., the pre-dose assessment on Day 1). 
In addition, the number and percentage of subjects with a change from baseline > 20 mmHg for 
systolic blood pressure and > 10 mmHg for diastolic blood pressure will be presented by 
treatment at each post-dose timepoint and at any post-dose timepoint.
12.3.5.7 Safety laboratory data
At each post-dose timepoint quantitative laboratory parameters will be summarised by 
treatment as absolute value and change from baseline using descriptive statistics and 95% CIs. 
Shift tables from baseline to the minimum and the maximum post-dose value, with regards to 
normal range, will be presented by treatment.


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 63/73
Urinalysis parameters will be presented in the listings.
12.3.6 Other variables
12.3.6.1 TG2 in plasma
At each post-dose timepoint, TG2 levels in plasma will be summarised using descriptive 
statistics by treatment as absolute value and change from baseline (i.e., the pre-dose assessment 
on Day 1) using descriptive statistics and 95% CIs.
Time profile plots will be presented by dose level, based on arithmetic means, and by subject, 
by showing the individual curves grouped by dose level (1 plot for each dose level) and ADA 
positivity/negativity (using different colours).
The TG2 levels in plasma obtained from healthy subjects will be summarised using descriptive 
statistics.
Box-plots summarising the pre-dose levels for treated subjects in the study, the healthy subjects’ 
external group, and each post-dose levels for the different doses for treated subjects will be 
presented. 
12.3.7 Interim analysis
Interim analysis not planned. 
13.
ETHICS COMMITTEE 
The study proposal will be submitted to the EC in accordance with the local requirements.
The EC shall give its opinion in writing, clearly identifying the study number, study title and 
ICF approved, before the clinical study commences.
A copy of all communications with the EC will be provided to the Sponsor.
The Investigator should provide written reports to the EC annually or more frequently if 
requested on any changes significantly affecting the conduct of the study and/or increasing risk 
to the subjects (according to the requirements of each country).
14.
 REGULATORY REQUIREMENTS
The study will be notified to the Health Authorities (or authorised by) according to the legal 
requirements.
Selection of the subjects will not start before the approval of the EC has been obtained and the 
study notified to Health Authorities (or authorised by).


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 64/73
15.
INFORMED CONSENT 
Informed consent must be written in a language understandable to the subjects. It is the 
responsibility of the Investigator to obtain written consent from each subject prior to any study 
related procedures taking place, by using the latest EC approved version of the document.
Adequate time shall be given to the subject to enquire to the Investigator about any clarification 
needed and to consider his or her decision to participate to the study.
If the subject is unable to read, the informed consent will be obtained in the presence of an 
impartial witness, e.g., a person independent of the study who will read and sign the ICF and 
the written information for the subject.
Consent must be documented by the subject’s dated signature. The signature confirms that the 
consent is based on information that has been understood. Moreover, the Investigator must sign 
and date the ICF.
Each subject’s signed informed consent must be kept on file by the Investigator. One copy must 
be given to the subject.
For subjects who agree to the collection of optional samples for transcriptomic analysis, 
separate informed consent must be obtained and the separate optional ICF signed prior to 
collection.
Female subjects becoming pregnant during the study and partner of a subject participating to 
the study becoming pregnant will have to sign a specific informed consent form to provide 
permission to Chiesi to collect information about the pregnancy, its outcome and the birth and 
health of the newborn child.
16.
SOURCE DOCUMENTS/DATA
16.1 Recording of Source Data
Data collection is the responsibility of the clinical study staff at the site under the supervision 
of the site Investigator. The Investigator is responsible for ensuring the accuracy, completeness, 
legibility, and timeliness of the data reported. All source documents should be completed in a 
neat, legible manner to ensure accurate interpretation of data. 
Data recorded in the eCRF transcribed from source documents should be consistent with the 
data recorded on the source documents.
16.2 Direct Access to Source Document/Data
The Investigators or designee must permit study-related monitoring, audits, EC review, or 
regulatory inspection, providing direct access to source data/documents.


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 65/73
17.
STUDY MONITORING
Monitoring will be performed by Fortrea who have been designated by Chiesi.
It is understood that the monitor(s) will contact and visit the Investigator/site before the study, 
regularly throughout the study and after the study had been completed, and that they will be 
permitted to inspect the various study records: case reports form, Investigator study file, and 
source data, provided that subject confidentiality is respected.
The purposes of these visits are:
to assess the progress of the study
to review the compliance with the study protocol
to discuss any emergent problem
to check the eCRFs for accuracy and completeness
to validate the contents of the eCRFs against the source documents
to assess the status of drug storage, dispensing, and retrieval.
Prior to each monitoring visit, the Investigator or staff will record all data generated since the 
last visit on the case report forms. The Investigator and/or study staff will be expected to be 
available for at least a portion of the monitoring visit to answer questions and to provide any 
missing information.
It is possible that the Investigator site may be audited by Sponsor personnel or regulatory 
national and/or international regulatory agencies during and after the study has been completed.
18.
QUALITY ASSURANCE
The R&D Quality Assurance Department of Chiesi may perform an audit at any time according 
to the Sponsor’s Standard Operating Procedures, in order to verify whether the study is being 
conducted in agreement with GCP and the protocol.
19.
INSURANCE AND INDEMNITY 
Chiesi holds and will maintain an adequate insurance policy covering damages arising out of 
Chiesi’s sponsored clinical research studies.
Chiesi will indemnify the Investigator and hold him/her harmless for claims for damages arising 
out of the investigation, in excess of those covered by his/her own professional liability 
insurance, providing that the study treatment was administered under his/her or deputy’s 
supervision and in strict accordance with accepted medical practice and with the study protocol.
The Investigator must notify Chiesi immediately upon notice of any claims or lawsuits.


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 66/73
20.
CONFIDENTIALITY
All study documents are provided by the Sponsor in confidence to the Investigator and his/her 
appointed staff. None of this material may be disclosed to any party not directly involved in the 
study without written permission from Chiesi.
The Investigator must assure the subject’s anonymity will be maintained. The Investigator will 
keep a separate list with at least the initials, the subject’s study numbers, names, and addresses 
and telephone numbers (if applicable). The Investigator will maintain this for the longest period 
of time allowed by his/her own institution and, in any case, until further communication from 
Chiesi.
21.
PREMATURE TERMINATION OF THE STUDY 
Both the Sponsor and the Investigator reserve the right to terminate the study at any time. 
Should this be necessary, the procedures for an early termination or temporary halt will be 
arranged after consultation by all involved parties.
The Sponsor should submit a written notification to the Regulatory Authorities concerned and 
EC providing the justification of premature ending or of the temporary halt.
22.
CLINICAL STUDY REPORT
The Clinical Study Report, including the statistical and clinical evaluations, shall be prepared 
and sent to Coordinating Investigator for agreement and signature.
At the end of the study a summary of the Clinical Study Report will be provided to all EC, to 
the Competent Authorities and to Investigators.
23.
RECORD RETENTION
After completion of the study, all documents and data relating to the study will be kept in an 
orderly manner by the Investigator in a secure study file.
Regulations require that essential documents must be retained for at least 2 years after the final 
marketing approval in an ICH region or until 2 years have elapsed since the formal interruption 
of the clinical development of the product under study.
It is the responsibility of the Sponsor to inform the Investigator of when these documents can 
be destroyed. The Investigator must contact Chiesi before destroying any study-related 
documentation. In addition, all subjects’ medical records and other source documentation will 
be kept for the maximum time permitted by the institution.
24.
PUBLICATION OF RESULTS
Chiesi is entitled to publish and/or present any results of this study at scientific meetings, and 
to submit the clinical study data to national and international Regulatory Authorities and, if they 


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 67/73
fall under the Chiesi commitments on Clinical Trial Transparency, to make them available on 
www.chiesi.com website.
Chiesi furthermore reserves the right to use such data for industrial purposes.
In the absence of a Study Steering Committee, Investigators will inform Chiesi before using the 
results of the study for publication or presentation and agree to provide the Sponsor with a copy 
of the proposed presentation. Data from individual clinical sites must not be published 
separately. 


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 68/73
25.
REFERENCES
[1] Raghu G, Remy-Jardin M, et al. Idiopathic Pulmonary Fibrosis (an Update) and 
progressive pulmonary fibrosis in adults. An Official ATS/ERS/JRS/ALAT Clinical 
Practice Guideline. Am J Respir Crit Care Med. Vol 205, Iss 9, pp e18-e47, May 1, 2022. 
[2] American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. 
International consensus statement. American Thoracic Society (ATS), and the European 
Respiratory Society (ERS). Am J Respir Crit Care Med. 2000;161:646–64. 
[3] American Thoracic Society/European Respiratory Society. International multidisciplinary 
consensus classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care 
Med. 2002;165:277–304. 
[4] Thomson CC, Duggal A, Bice T, Lederer DJ, Wilson KC, Raghu G. Clinical practice 
guideline summary for clinicians: diagnosis of idiopathic pulmonary fibrosis. Ann Am 
Thorac Soc. 2019;16(3):285–90. 
[5] Raghu G, Rochwerg B, Zhang Y, Garcia CAC, Azuma A, Behr J, et al. An official 
ATS/ERS/JRS/ALAT clinical practice guideline: Treatment of idiopathic pulmonary 
fibrosis. An update of the 2011 clinical practice guideline. Am J Respir Crit Care Med. 
2015;192:e3–19. 
[6] Tang J, Huang H, Ji X, Zhu X, Li Y, She M, et al. Involvement of IL 13 and tissue 
transglutaminase in liver granuloma and fibrosis after schistosoma japonicum infection. 
Mediators Inflamm. 2014;75348. 
[7] Olsen KC, Sapinoro RE, Kottmann RM, Kulkarni AA, Iismaa SE, Johnson GVW, et al. 
Transglutaminase 2 and its role in pulmonary fibrosis. Am J Respir Crit Care Med. 
2011;184:699–707. 
[8] Zhao G, Zhang ZQ, Zhang B, Luo M, Sun YW, Wu ZY. Down-regulation of tTG 
expression by RNAi inhibits HSC proliferation and attenuates liver fibrosis. Int J Clin Exp 
Pathol. 2011;4(5):513–520. 
[9] Huang L, Haylor JL, Hau Z, Jones RA, Vickers ME, Wagner B, et al. Transglutaminase 
inhibition ameliorates experimental diabetic nephropathy. Kidney Int. 2009;76(4):383–94. 
[10]
Shweke N, Boulos N, Jouanneau C, Vandermeersch S, Melino G, Dussaule JC, et al. 
Tissue transglutaminase contributes to interstitial renal fibrosis by favoring accumulation 
of fibrillar collagen through TGF beta activation and cell infiltration. Am J Pathol. 
2008;173(3):631–42. 
[11]
Johnson TS, Fisher M, Haylor JL, Hau Z, Skill NJ, Jones R, et al. Transglutaminase 
inhibition reduces fibrosis and preserves function in experimental chronic kidney disease. 
J Am Soc Nephrol. 2007;18(12):3078–88. 


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 69/73
[12]
Nardacci R, Iacono OL, Ciccosanti F, Falasca L, Addesso M, Amendola A, et al. 
Transglutaminase type II plays a protective role in hepatic injury. Am J Pathol. 
2003;162(4):1293–303. 
[13]
Small K, Feng JF, Lorenz J, Donnelly ET, Yu A, Im MJ, et al. Cardiac specific 
overexpression of transglutaminase II (G(h)) results in a unique hypertrophy phenotype 
independent of phospholipase C activation. J Biol Chem. 1999;274(30):21291–6. 
[14]
Chiesi Farmaceutici S.p.A. Investigator’s Brochure: CHF10067. 2021. 
[15]
Bavbek S., Pagani M., Alvarez-Cuesta E, et al., Hypersensitivity reactions to 
biologicals: 
An 
EAACI 
position 
paper. 
Allergy. 
2022; 
77.39 
– 
54. 
https://doi.org/10.1111/all.14984.
[16]
Clinical Trials Facilitation and Coordination Group. Recommendations related to 
contraception and pregnancy testing in clinical trials (Version 1.1). 2020. 
[17]
William D Travis, Ulrich Costabel, David M Hansell, Talmadge E King Jr, David A 
Lynch, Andrew G Nicholson, et al. An official American Thoracic Society/European 
Respiratory Society statement: Update of the international multidisciplinary classification 
of the idiopathic interstitial pneumonias. 15. 2013;188(6):733–48. 
[18]
Brown SGA. Clinical features and severity grading of anaphylaxis. J Allergy Clin 
Immunol. 2004;114(2):371–6. 
[19]
Sampson HA, Muñoz-Furlong A, Campbell RL, Jr NFA, Bock SA, Branum A, et al. 
Second symposium on the definition and management of anaphylaxis: summary report--
Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis 
Network symposium. J Allergy Clin Immunol. 2006 Feb;117(2):391–7. 
[20]
Graham BL, Steenbruggen I, Miller MR, Barjaktarevic IZ, Cooper BG, Hall GL, et al. 
Standardization of Spirometry 2019 Update. An Official American Thoracic Society and 
European Respiratory Society Technical Statement. Am J Respir Crit Care Med. 
2019;200(8):e70–88. 
[21]
Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL, Culver BH, et al. Multi-ethnic 
reference values for spirometry for the 3-95-yr age range: the global lung function 2012 
equations. Eur Respir J. 2012;40(6):1324–43. 
[22]
Graham BL, Brusasco V, Burgos F, Cooper BG, Jensen R, Kendrick A, et al. 2017 
ERS/ATS standards for single-breath carbon monoxide uptake in the lung. Eur Respir J. 
2017;49. 
[23]
Common Terminology Criteria for Adverse Events (CTCAE; Version 5.0). National 
Cancer Institute; 2017. 


Clinical Study Protocol
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 70/73
[24]
European Medicines Agency. Guideline on the Investigation of Bioequivalence 
(CPMP(EWP/QWP/1401/98 Rev. 1/Corr.) [Internet]. European Medicines Agency; 2010. 
Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-
investigation-bioequivalence-rev1_en.pdf


Clinical Study Protocol – Appendix 1
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 71/73
APPENDIX 1 - APPROVAL OF THE PROTOCOL BY 
COORDINATING CLINICAL INVESTIGATOR
A PHASE IB, RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED 
STUDY TO INVESTIGATE THE SAFETY, TOLERABILITY, AND 
PHARMACOKINETICS OF AN INTRAVENOUS MONOCLONAL ANTIBODY 
(MAB) AFTER SINGLE ASCENDING DOSES IN SUBJECTS AFFECTED BY 
IDIOPATHIC PULMONARY FIBROSIS
Product: CHF10067 
Pharmaceutical Form: Solution for intravenous infusion
Approval of Clinical Study Protocol by the Investigator: 
I have carefully read this protocol and I agree that it contains all the necessary information 
required to conduct the study and I agree to conduct it as described.
I understand that this study will not be initiated without Ethics Committee approvals and that 
the administrative requirements of the governing body of the institution will be fully complied 
with.
Informed written consent will be obtained from all participating subjects and appropriately 
documented, prior to their enrolment in the study. 
The undersigned agrees that the study will be carried out in conformity with the Declaration of 
Helsinki (as applicable, with attention being drawn to Section concerning freely given consent), 
ICH E6 Good Clinical Practices and with all the other local laws and regulations relevant to the 
use of new and approved therapeutic agents in subjects.
Coordinating Investigator’s Name and Qualifications: ______________________, ______
Centre No.: 
_____________________
          Signature
Date
Chiesi Farmaceutici S.p.A.
Via Palermo 26/A
43122 Parma - Italy


Clinical Study Protocol – Appendix 2
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 72/73
APPENDIX 2 - APPROVAL OF THE PROTOCOL BY 
CLINICAL INVESTIGATOR(S)
A PHASE IB, RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED 
STUDY TO INVESTIGATE THE SAFETY, TOLERABILITY, AND 
PHARMACOKINETICS OF AN INTRAVENOUS MONOCLONAL ANTIBODY 
(MAB) AFTER SINGLE ASCENDING DOSES IN SUBJECTS AFFECTED BY 
IDIOPATHIC PULMONARY FIBROSIS
Product: CHF10067 
Pharmaceutical Form: Solution for intravenous infusion
Approval of Clinical Study Protocol by the Investigator: 
I have carefully read this protocol and I agree that it contains all the necessary information 
required to conduct the study and I agree to conduct it as described.
I understand that this study will not be initiated without Ethics Committee approvals and that 
the administrative requirements of the governing body of the institution will be fully complied 
with.
Informed written consent will be obtained from all participating subjects and appropriately 
documented, prior to their enrolment in the study. 
The undersigned agrees that the study will be carried out in conformity with the Declaration of 
Helsinki (as applicable, with attention being drawn to Section concerning freely given consent), 
ICH E6 Good Clinical Practices and with all the other local laws and regulations relevant to the 
use of new and approved therapeutic agents in subjects.
Investigator’s Name and Qualifications: ______________________, ______
Centre No.: 
__________________________
       Signature
Date
Chiesi Farmaceutici S.p.A.
Via Palermo 26/A
43122 Parma - Italy
 


Clinical Study Protocol – Appendix 3
Clinical Study Code No.: CLI-10067AA1-01
Version No.: 6.0
EUDRACT No.: 2022-001079-15
Date: 06 July 2023
CONFIDENTIAL
Page 73/73
APPENDIX 3 - RECOMMENDATIONS RELATED TO 
CONTRACEPTION AND PREGNANCY TESTING IN 
CLINICAL STUDIES
Definition of female of childbearing potential and of fertile men
For the purpose of this document, a woman is considered of childbearing potential (WOCBP), i.e., fertile, 
following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation 
methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy.
A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high 
follicle-stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal 
state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 
12 months of amenorrhea, a single FSH measurement is insufficient.
For the purpose of this document, a man is considered fertile after puberty unless permanently sterile by bilateral 
orchidectomy.
Birth control methods, which may be considered as highly effective
For the purpose of this guidance, methods that can achieve a failure rate of less than 1% per year when used 
consistently and correctly are considered as highly effective birth control methods. Such methods include:
• combined (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation:

oral

intravaginal

transdermal
• progestogen-only hormonal contraception associated with inhibition of ovulation:

oral

injectable

implantable 3
• intrauterine device  3
• intrauterine hormone-releasing system3
• bilateral tubal occlusion 3
• vasectomised partner 1, 3
• sexual abstinence 2
1 Vasectomised partner is a highly effective birth control method provided that partner is the sole sexual partner of 
the WOCBP study subject and that the vasectomised partner has received medical assessment of the surgical 
success.
2 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 treatments. The reliability of sexual abstinence 
needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the 
subject.
3 Methods with low-user dependency
Clinical Trial Facilitation Group guidance: Recommendations related to contraception and pregnancy 
testing in clinical trials. Final version 1.1, 21/09/2020.

SAP_001.pdf: 
 
 
 
Page 1 of 65 
 
STATISTICAL ANALYSIS PLAN 
 
A Phase Ib, randomised, double-blind, placebo-controlled study to 
investigate the safety, tolerability, and pharmacokinetics of an 
intravenous monoclonal antibody (mAb) after single ascending 
doses in subjects affected by idiopathic pulmonary fibrosis 
 
Protocol: CLI-10067AA1-01 
SGS Internal 
Reference: 
 
Development phase: Ib 
Sponsor: Chiesi Farmaceutici S.p.A. 
SAP version number: Final 1.0  
SAP version date: 30MAY2024 
NCT05513950


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 2 of 65 
TABLE OF CONTENTS 
Table of contents .......................................................................................................... 2 
Protocol history ............................................................................................................ 6 
List of abbreviations .................................................................................................... 7 
Definition of terms ..................................................................................................... 10 
1. 
Introduction ....................................................................................................... 11 
1.1 
Study objectives............................................................................................. 11 
1.2 
Study design .................................................................................................. 11 
1.3 
Expected sample size ..................................................................................... 12 
1.4 
Randomisation and blinding .......................................................................... 12 
1.5 
Interim analysis ............................................................................................. 12 
1.6 
Software ......................................................................................................... 12 
1.7 
Validation model ........................................................................................... 13 
2. 
Pharmacokinetic, and immunogenicity analyses ............................................ 14 
2.1 
Pharmacokinetic analyses .............................................................................. 14 
2.1.1 
Available data .................................................................................. 14 
2.1.2 
Endpoints and derivation rules ........................................................ 14 
2.1.3 
Inferential statistics ......................................................................... 15 
2.1.4 
Presentation of results ..................................................................... 15 
2.2 
Immunogenicity ............................................................................................. 17 
2.2.1 
Available data .................................................................................. 17 
2.2.2 
Derivation rules ............................................................................... 19 
2.2.3 
Presentation of results ..................................................................... 19 
3. 
Safety analyses ................................................................................................... 21 
3.1 
Adverse events............................................................................................... 21 
3.1.1 
Available data .................................................................................. 21 
3.1.2 
Derivation rules ............................................................................... 21 
3.1.3 
Presentation of results ..................................................................... 22 
3.2 
Clinical laboratory evaluation ....................................................................... 23 
3.2.1 
Available data .................................................................................. 23 
3.2.2 
Derivation rules ............................................................................... 23 
3.2.3 
Presentation of results ..................................................................... 24 
3.3 
Vital signs ...................................................................................................... 24 
3.3.1 
Available data .................................................................................. 24 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 3 of 65 
3.3.2 
Derivation rules ............................................................................... 25 
3.3.3 
Presentation of results ..................................................................... 25 
3.4 
Electrocardiograms ........................................................................................ 25 
3.4.1 
Available data .................................................................................. 25 
3.4.2 
Derivation rules ............................................................................... 26 
3.4.3 
Presentation of results ..................................................................... 26 
3.5 
Lung function ................................................................................................ 26 
3.5.1 
Available data .................................................................................. 26 
3.5.2 
Presentation of results ..................................................................... 27 
3.6 
Systemic markers for evaluation of immediate hypersensitivity reactions ... 27 
3.6.1 
Available data .................................................................................. 27 
3.6.2 
Presentation of results ..................................................................... 27 
3.7 
Physical examinations ................................................................................... 27 
4. 
Other variables................................................................................................... 28 
4.1 
TG2 in plasma ............................................................................................... 28 
4.1.1 
Available data .................................................................................. 28 
4.1.2 
Presentation of results ..................................................................... 28 
5. 
General characteristics analyses ...................................................................... 29 
5.1 
Subject disposition......................................................................................... 29 
5.2 
Important protocol deviations and eligibility ................................................ 29 
5.3 
Demographic and other baseline characteristics ........................................... 29 
5.3.1 
Available data .................................................................................. 29 
5.3.2 
Derivation rules ............................................................................... 30 
5.3.3 
Presentation of results ..................................................................... 30 
5.4 
Medical history and concomitant diseases .................................................... 30 
5.4.1 
Available data .................................................................................. 30 
5.4.2 
Derivation rules ............................................................................... 30 
5.4.3 
Presentation of results ..................................................................... 30 
5.5 
Procedures and Medications .......................................................................... 31 
5.5.1 
Available data .................................................................................. 31 
5.5.2 
Derivation rules ............................................................................... 31 
5.5.3 
Presentation of results ..................................................................... 31 
5.6 
Exposure to study treatment .......................................................................... 32 
5.6.1 
Available data .................................................................................. 32 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 4 of 65 
5.6.2 
Presentation of results ..................................................................... 32 
6. 
General methodology......................................................................................... 33 
6.1 
Analysis sets .................................................................................................. 33 
6.1.1 
Analysis sets .................................................................................... 33 
6.1.2 
As planned versus as actual analysis ............................................... 33 
6.1.3 
Exclusion of data from the statistical analyses ................................ 33 
6.1.3.1 
Exclusion of data from PK analysis ......................................................... 34 
6.1.3.2 
Exclusion of data from safety analysis ..................................................... 36 
6.2 
Phases and time points................................................................................... 36 
6.2.1 
Phases .............................................................................................. 36 
6.2.2 
Baseline and change from baseline ................................................. 37 
6.2.3 
Relative day ..................................................................................... 37 
6.2.4 
Analysis visits ................................................................................. 37 
6.2.5 
Worst-case ....................................................................................... 41 
6.3 
Imputation and rounding rules ....................................................................... 41 
6.3.1 
Missing values ................................................................................. 41 
6.3.2 
Handling partially or completely missing dates in calculations ...... 42 
6.3.3 
Values below or above a threshold ................................................. 42 
6.3.4 
Rounding of derived variables ........................................................ 42 
6.3.5 
Outliers ............................................................................................ 42 
6.4 
Presentation of results.................................................................................... 43 
6.4.1 
Calculation of descriptive statistics and percentages ...................... 43 
6.4.2 
Presentation of treatments ............................................................... 44 
6.4.3 
Ordering in tables, listings and figures ............................................ 44 
6.4.4 
Raw SAS output .............................................................................. 44 
6.4.5 
eCTD tables ..................................................................................... 44 
7. 
Changes to the planned analysis ....................................................................... 46 
7.1 
Changes not covered by protocol amendments before unblinding ............... 46 
8. 
References ........................................................................................................... 48 
9. 
List of tables, listings and figures ..................................................................... 49 
9.1 
Tables ............................................................................................................ 49 
9.2 
Listings .......................................................................................................... 55 
9.3 
Figures ........................................................................................................... 60 
10. Appendices ......................................................................................................... 62 
10.1 
SAS code ....................................................................................................... 62 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 5 of 65 
10.2 
Schedule of assessments ................................................................................ 63 
10.3 
Dictionary versions ........................................................................................ 65 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 6 of 65 
PROTOCOL HISTORY 
 
Protocol: 
Version or ID 
Date 
(ddMMMyyyy) 
Impact of the changes on the statistical 
analysis 
Final 1.0 
03MAY2022 
NAP 
Final 2.0 
25AUG2022 
NAP 
Final 3.0 
24OCT2022 
NAP 
Final 4.0 
22MAY2023 
NAP 
Final 5.0 
16JUN2023 
NAP 
Final 6.0 
06JUL2023 
NAP 
 
Protocol amendments: 
Version or ID 
Date 
(ddMMMyyyy) 
Impact of the amendment on the 
statistical analysis 
NAP 
 
 
This statistical analysis plan (SAP) only considers the latest version of the protocol, 
and of the protocol amendments, as listed above. 
 
 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 7 of 65 
LIST OF ABBREVIATIONS 
Ab-HCV 
hepatitis C virus antibody 
Ab-HIV1 
human immunodeficiency virus 1 antibody 
Ab-HIV2 
human immunodeficiency virus 2 antibody 
ADA 
anti-drug antibodies 
ADaM 
analysis data model 
ADR 
adverse drug reaction 
AE 
adverse event 
anti-HBc 
hepatitis B core antibody 
ATC 
anatomical therapeutic chemical 
AUC 
area under the concentration-time curve 
AUC0-t 
area under the concentration-time curve, from 0 to the last 
quantifiable concentration 
AUCinf 
area under the concentration-time curve, extrapolated to infinity 
BLQ 
below the limit of quantification 
BMI 
body mass index 
bpm 
beats per minute 
Cinf 
concentration at the end of infusion 
CI 
confidence interval 
CL 
clearance 
Cmax 
maximum observed concentration 
eCRF 
electronic case report form 
CV 
coefficient of variation 
DBP 
diastolic blood pressure 
DLCO 
diffusing capacity of the lung for carbon monoxide 
DRM 
data review meeting 
DRR 
data review report 
DY 
relative day 
ECG 
Electrocardiogram 
EMA 
European Medicines Agency 
ENR 
enrolled set 
FEV1 
forced expiratory volume in 1 second 
FSH 
follicle-stimulating hormone 
FVC 
forced vital capacity 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 8 of 65 
HBsAG 
hepatitis B surface antigen 
HIV1 
human immunodeficiency virus 1 
HIV2 
human immunodeficiency virus 2 
HR 
heart rate 
ICF 
informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use 
IHR 
Immediate Hypersensitivity Reaction 
IL 
Interleukin 
IPF 
idiopathic pulmonary fibrosis 
IRT 
interactive responsive technology 
IS 
immunogenicity 
IV 
intravenous 
KFR 
key first result 
mAb 
monoclonal antibody 
MedDRA 
Medical Dictionary for Regulatory Activities 
nAb 
neutralising antibody 
NAP 
not applicable 
PCR 
polymerase chain reaction 
PK 
pharmacokinetic 
QTc 
corrected QT interval 
QTcF 
Fridericia’s corrected QT interval 
RNA 
ribonucleic acid 
RND 
randomised set 
SAF 
safety set 
SAP 
statistical analysis plan 
SBP 
systolic blood pressure 
SD 
standard deviation 
SDTM 
study data tabulation model 
SOP 
standard operating procedure 
STAT 
Statistics 
t1/2 
terminal half-life 
TEAE 
treatment-emergent adverse event 
TG2 
transglutaminase 2 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 9 of 65 
TLF 
tables, listings and figures 
tmax 
time to Cmax 
tinf 
time to Cinf 
TNF-α 
tumour necrosis factor-α 
UIP 
usual interstitial pneumonia 
VS 
vital signs 
Vz 
volume of distribution 
WBC 
white blood cell 
WHO 
World Health Organisation 
WHODrug 
WHO drug dictionary 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 10 of 65 
DEFINITION OF TERMS 
bias 
The systematic tendency of any factors associated with the design, 
conduct, analysis and evaluation of the results of a clinical trial to 
make the estimate of a treatment effect deviate from its true value. 
Bias introduced through deviations in conduct is referred to as 
‘operational’ bias. The other sources of bias listed above are 
referred to as ‘statistical’. 
 
 
case report form 
(CRF) 
A printed, optical, or electronic document designed to record 
protocol required information to be reported to the sponsor for each 
trial subject. 
 
 
display 
Analysis table, listing or figure 
 
 
missing data 
Data that would be meaningful for the analysis of a given endpoint 
but were not collected. They should be distinguished from data that 
do not exist. 
 
 
phase 
Interval of time in the planned conduct of a study associated with a 
specific purpose: for example, screening, treatment, follow-up. 
 
 
significant digit 
All digits of a number used to express it to the required degree of 
accuracy, starting from the first non-zero digit. 
 
 
standardised 
unit 
unit populating --STRESU in the clinical database 
 
 
treatment-
emergent 
abnormality 
Any postbaseline abnormality/toxicity that was not present at 
baseline (e.g., glucose low at baseline and high post-baseline; QTcF 
]450; 480] ms at baseline and >500 ms post-baseline) 
 
 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 11 of 65 
1. 
INTRODUCTION 
This SAP describes the final statistical analysis to be performed for the 
CLI-10067AA1-01 (
) study. 
This SAP covers the pharmacokinetic (PK), immunogenicity (IS), safety, 
transglutaminase 2 (TG2) levels, and general characteristics parts of the statistical 
analysis. It specifies the analysis displays to be presented and describes the methods 
and procedures in a more elaborated way than in the statistical methods section of the 
protocol. 
The statistical analysis will process and present the results following the International 
Council for Harmonisation of Technical Requirements for Pharmaceuticals for 
Human Use (ICH) standards. 
1.1 
STUDY OBJECTIVES 
According to the protocol, the primary objective of this study is: 
• to assess the safety and tolerability of single ascending doses of 
CHF10067 in subjects with IPF. 
According to the protocol, the secondary objectives of this study are: 
• to evaluate the CHF10067 PK profile in serum; 
• to evaluate the CHF10067 immunogenicity profile in terms of anti-drug 
antibody (ADA) and neutralising antibody (nAb). 
According to the protocol, the exploratory objective of this study is: 
• to evaluate TG2 levels in plasma. 
1.2 
STUDY DESIGN 
This is a Phase Ib, multi-centre, multi-country, randomised, double-blind, placebo-
controlled study to investigate the safety, tolerability, immunogenicity, and PK of 
single IV doses of CHF10067 in subjects with IPF. The effect of CHF10067 on TG2 
levels will also be investigated as an exploratory endpoint. 
Overall, 24 subjects will be enrolled in 3 cohorts (Cohorts A [1000 mg], B 
[anticipated 2000 mg], and C [anticipated 3000 mg]) consisting of 8 subjects per 
cohort. In each cohort, 6 subjects will receive CHF10067, and 2 subjects will receive 
placebo. 
The doses will be administered according to an escalation scheme designed to ensure 
sufficient safety conditions for subjects. In each cohort, subjects will be divided into 2 
sub-groups, with each sub-group being dosed at least 24 hours apart. The first 
sub-group will comprise 2 subjects, with 1 subject receiving CHF10067 and 1 subject 
receiving placebo. The second sub-group will comprise 6 subjects, with 5 subjects 
receiving CHF10067 and 1 subject receiving placebo. Continuation to dose the 
remaining 6 subjects will be evaluated by at least the Medical Monitor and Sponsor 
Clinical Research Physician based on the safety data provided by the Investigator(s) 
where the first-sub-group have been dosed. The decision to escalate to the next dose 
will be made by the Safety Advisory Committee when safety data until Day 14 have 
been collected for all subjects at the previous dose level. Pharmacokinetic and 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 12 of 65 
immunogenicity data will also be included in the safety evaluation for dose escalation 
(if available) but are not mandatory to escalate to the next dose. 
An overview of the study design is shown in the figure below. 
 
The schedule of assessments is in appendix 10.1. 
1.3 
EXPECTED SAMPLE SIZE 
This study is designed to explore the safety and tolerability of CHF10067 for the first 
time in subjects affected by IPF, while exposing a minimum number of subjects; 
therefore, no formal power calculation was performed. 
A sample size of 24 subjects (8 subjects per cohort; 6 treated with CHF10067 and 2 
with placebo) is deemed adequate to assess safety and tolerability of CHF10067. In 
each cohort, a minimum of 2 subjects are required to be not receiving antifibrotic 
treatment (including subjects with previous use of antifibrotic treatment that has been 
stopped for at least 2 weeks prior to screening). 
1.4 
RANDOMISATION AND BLINDING 
An interactive responsive technology (IRT) system will be used for randomisation 
and assignment to blind treatment (CHF10067 or placebo). 
The Investigator, or designee, at the sites will use the IRT system to screen and 
randomise subjects and to assign treatment kits according to the randomisation list. 
Subjects will be randomised in a 3:1 ratio within each cohort to receive either 
CHF10067 or placebo. Randomisation will require a minimum of 2 subjects within 
each cohort not receiving antifibrotic treatment (including subjects with previous use 
of antifibrotic treatment that has been stopped for at least 2 weeks prior to screening). 
In each cohort, at least 24 hours must elapse between dosing of the first 2 subjects (1 
CHF10067; 1 placebo) and the remaining 6 subjects. The IRT system will be used to 
coordinate the scheduling of Day 1 visits to be sure that this procedure is followed. 
1.5 
INTERIM ANALYSIS 
No interim analyses are foreseen. 
1.6 
SOFTWARE 
SAS version 9.4 (SAS Institute Inc., Cary, NC, USA) will be used for programming. 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 13 of 65 
Phoenix WinNonlin 8.3 or later (Certara, NJ, USA) will be used for calculations of 
PK parameters.  
1.7 
VALIDATION MODEL 
SGS Statistics (STAT) and Pharmacokinetics (PK) standard operating procedures 
(SOPs) and work instructions (WIs) as effective at the time of the activity will be 
followed throughout the project, provided the applicable regulatory requirements are 
still met. 
The analysis tables/figures/listings will be reviewed by an independent person 
(validated according to model B; see SOP.STAT.020 and SOP.PK.020). 
PK analysis will be validated according SOP.PK.001. 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 14 of 65 
2. 
PHARMACOKINETIC, AND IMMUNOGENICITY 
ANALYSES 
2.1 
PHARMACOKINETIC ANALYSES 
2.1.1 
Available data 
Blood samples will be collected for the determination of CHF10067 in serum at the 
following time points: pre-dose (within 75 minutes from start of infusion), at the end 
of infusion, and 2, 4, 8, and 20 hours after the end of the infusion and 5, 7, 14, 28, 56 
and 84 days post-dose. 
2.1.2 
Endpoints and derivation rules 
The following PK parameters will be derived for serum CHF10067:  
• AUC0-t, AUCinf, Cmax, tmax, Cinf, tinf, CL, Vz, t1/2. 
Standard non-compartmental methods will be used for the calculation of the PK 
parameters from the individual serum concentration – time profiles using actual 
sampling time points from start of infusion. If actual sampling time is not available, 
nominal time will be used (see also section 6.1.3.1). The analysis will consider time 
only in hours and minutes. Any seconds in the time part of a record will be imputed 
by zero. The area under the serum concentration-time curve (AUC)  will be calculated 
according to the linear trapezoidal method. 
PK parameters definition 
• AUC0-t: AUC from 0 to the last quantifiable concentration; 
• AUCinf: AUC from 0 to infinite time calculated as:AUC extrapolated to 
infinity will be calculated as the sum of AUC0-t and a residual part 
extrapolated to infinite time. The residual area from the last 
concentration data point to infinite time is calculated using the 
approximation: 
∫𝐶𝑡𝑑𝑡= 𝐶𝑡𝜆𝑧
⁄
∞
𝑡
 
where λz is the first order terminal rate constant, estimated by linear 
regression of the terminal loglinear segment of the plasma log 
concentration curve, and Ct is the last quantifiable concentration data 
point; 
• Cmax and tmax: the value and time of the maximum serum concentration 
will be obtained directly from the experimental data without 
interpolation; 
• Cinf and tinf: the value and time of the serum concentration at end of 
infusion; 
• CL: clearance will be calculated as: 
𝐷𝑜𝑠𝑒𝐴𝑈𝐶𝑖𝑛𝑓
⁄
 
• Vz: volume of distribution will be calculated as: 
𝐷𝑜𝑠𝑒(𝜆𝑧∗ 𝐴𝑈𝐶𝑖𝑛𝑓)
⁄
 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 15 of 65 
• t1/2: terminal half-life, associated with negative slope (-λz), will be 
calculated as 0.693/λz from the individual drug concentration time 
profiles 
Criteria for t1/2 estimation 
• At least three time points (excluding tmax) should be used for the 
determination of the elimination rate constant (z), otherwise the t1/2 as 
well as the derived parameters (AUCinf, CL and Vz) cannot be estimated 
and will be presented as “NE” (not estimated) in the tables.  
• The adjusted correlation coefficient of the linear regression should be 
≥0.85, otherwise the t1/2 as well as the derived parameters (AUCinf, CL 
and Vz) are not reliably estimated and will not be reported (presented as 
“NR” (not reported) in the tables). 
Criteria for AUCinf estimation 
• When for a profile the AUCextrapolated / AUC0-∞ > 20%, this AUCinf as 
well as the derived parameters (CL and Vz) will be excluded from the 
statistical analyses. 
All PK parameters will be estimated, if feasible, and presented in the TLFs, unless 
specified differently (e.g., unreliable t1/2). PK parameters that cannot be estimated will 
be specified in the Data Review Report (DRR) (prior to database lock and disclosure 
of the bioanalytical data) and/or PK DRR (after database lock and disclosure of the 
bioanalytical data). PK data that is excluded from PK analysis will be discussed in the 
DRR and/or PK DRR, and marked in the relevant tables, accompanied with a 
footnote. 
2.1.3 
Inferential statistics 
Dose proportionality in terms of CHF10067 AUC0-t, AUCinf, and Cmax will be 
evaluated using the power model, including the log-transformed PK parameters as 
dependent variables, and the log-transformed CHF10067 dose as a covariate. The 
slope for log-transformed dose will be estimated with its 90% confidence interval 
(CI) to examine dose proportionality. 
There will be no evidence for deviation of dose proportionality in case the 90% CI of 
the fixed slope for log-dose contains 1. 
SAS code is provided in section 10.1. 
2.1.4 
Presentation of results 
Listing 
The actual sampling date/time and the actual time of end of infusion will be listed per 
subject, dose level and analysis time point. For samples that are reallocated to another 
analysis time point window, the new analysis time point window will be presented in 
“Analysis Time Window” column. Additionally, individual PK concentrations will be 
presented. PK concentrations excluded from PK parameter estimation and/or 
descriptive statistics will be marked and clarified with a remark. Important time 
deviations will be reported with elapsed time from planned timepoint in “Remarks” 
column. 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 16 of 65 
Subjects that are excluded from the PK set and/or PK data that is excluded from PK 
parameter estimation, descriptive statistics and/or inferential statistics will be listed 
per subject, dose level and concentration time point or PK parameter, with the reason 
for exclusion. If this reason is due to an important protocol deviation, it will be 
marked too.   
Tables 
Individual actual sampling time points relative to end of infusion will be tabulated, 
per dose level. Important time deviations will be marked in the table with appropriate 
footnoting. Missing sampling times will be reported as “NT” (no time). Missing 
samples will be reported as “NS” (no sample). 
Individual serum concentration data together with descriptive statistics will be 
tabulated, per dose level at each allocated analysis time point window. A footnote 
will be added to specify that a time windowing approach was considered to assign 
samples to the analysis time point. Missing samples or samples missing in an analysis 
time point window due to reallocated to another analysis time point window will be 
reported as “NRS” (no sample or reallocated sample). Samples for which no result is 
available will be reported as “NR” (no result). Exclusion of PK concentrations from 
descriptive statistics is described in section 6.1.3.1. 
Individual PK parameters together with descriptive statistics will be tabulated, per 
dose level. Not estimable PK parameters will be reported as “NE” (not estimated). 
Exclusion of PK parameters from descriptive statistics is described in section 2.1.2 
and section 6.1.3.1. 
For the dose proportionality assessment on CHF10067 AUC0-t, AUCinf, and Cmax, the 
slope and 90% CI of the power model will be tabulated. 
Figures 
Serum concentration - time profiles will be presented in linear/linear and log/linear 
scales. Mean (±SD for linear/linear scale) graphs will be presented with all dose 
levels on the same graph. Individual graphs will be presented per dose level, with all 
subjects on the same graph. The graphs will be presented over the full-time scale (i.e., 
up to Day 84). 
The following attributes will be used in the concentration – time profiles: 
- 
Dose levels (mean graphs) 
o A different colour, line pattern and symbol per dose level. 
- 
Subjects (individual graphs with all subjects on the same graph, i.e., spaghetti 
plot) 
o A different line pattern and symbol per subject, and a unique colour 
for ADA positivity or negativity (see definitions in Section 2.2.2). 
The individual and geometric mean values (log-transformed) of CHF10067 AUC0-t, 
AUCinf, and Cmax will be presented graphically versus log-transformed dose. In 
addition, the linear regression line fitted will be displayed on each plot. The 
individual values will have the same colour and symbol as used in the concentration – 
time profiles. Only individual values used in the analysis will be plotted. 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 17 of 65 
2.2 
IMMUNOGENICITY 
2.2.1 
Available data 
Serum samples for anti-drug antibody (ADA) assessments will be conducted utilizing 
a tiered approach (i.e., screen, confirm, titer), and ADA data will be collected 
pre-dose and at Days 14, 28, 56, and 84 and in case of early termination visit. 
ADA result from each sample will be reported as either: 
• ADA-positive: when ADA is detected at both screening and 
confirmatory tests in a sample, the sample is considered positive. 
• ADA-negative: when ADA is not detected at screening test OR ADA is 
detected at screening but not detected at confirmatory test, the sample is 
considered negative. 
• ADA-unevaluable: when a sample could not be tested for ADA status 
(“un-assayed sample”) due to inadequate sample volume, mishandling, 
or errors in sample collection, processing, storage, etc. ..., either at 
screening or confirmatory test. 
If the confirmatory sample is positive (i.e., ADA-positive sample), the ADA titer will 
be reported as well. ADA titer is a quasi-quantitative expression of the level of ADA 
in the sample. 
In addition, the presence of neutralizing antibody (nAb) will be tested for all 
ADA -positive samples using a ligand-binding assay. The nAb results will be 
reported as either positive or negative. 
 
 




Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 19 of 65 
2.2.2 
Derivation rules 
No data imputation will be performed for missing and/or unevaluable samples. 
Using the sample ADA status, subjects will be classified using the following 
definitions: 
• ADA evaluable subject: A subject with baseline sample and at least one 
sample taken after drug administration during the treatment periods that 
are appropriate for ADA testing (i.e., with reportable result). 
• ADA unevaluable subject: A subject without an evaluable sample at 
baseline OR with reportable baseline result but without a single sample 
taken (or without a reportable result) after drug administration during 
the treatment period. 
• ADA-positive subject (ADA+): A subject with at least one treatment-
induced or treatment-boosted ADA-positive sample at any time during 
the treatment period. See definitions of treatment-induced and 
treatment-boosted ADA in Section 2.2.3. 
• ADA-negative subject (ADA-): A subject without a treatment-induced 
or treatment-boosted ADA-positive sample during the treatment period. 
2.2.3 
Presentation of results 
The number and percentage of subjects who fulfil the below criteria will be presented 
by treatment. 
• Baseline ADA-positive 
For this group of subjects, titer range (median and interquartile range 
(IQR)) of the baseline ADA-positive samples will be reported. 
• ADA positive at any visit (ADA prevalence) 
A subject with at least one positive ADA result available at any time, 
including baseline (i.e., pre-existing ADA) and post-baseline 
measurements (i.e., ADA+). For this group of subjects, peak positive 
titer and range (median, IQR) will be reported. 
• ADA incidence 
o Treatment-induced ADA, defined as ADA developed de novo 
(seroconversion) following drug administration (i.e., formation of 
positive ADA any time after the drug administration in subjects 
with ADA-negative baseline). 
For this group of subjects, the following additional parameters will 
be presented:  
- 
Peak positive titer and range (median, IQR); 
- 
Onset of ADA 
Time to onset of ADA (i.e., time period between the initial 
administration of the drug and the first instance of 
treatment-induced ADA); 
- 
Duration of ADA 
o Persistently positive ADA 
Subjects having a treatment-induced ADA detected at 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 20 of 65 
least two non-consecutive time points, with the last 
ADA-positive measurement (irrespective of any 
negative samples in between first and last positive 
measurements) being detected at the end of the study 
period (i.e., day 84) for completer subjects or at the last 
available sampling time point for prematurely 
discontinued subjects. 
o Transiently positive ADA 
Subjects having a treatment-induced ADA not fulfilling 
the above condition for persistently positive. 
o Treatment-boosted ADA, defined as a baseline positive ADA titer 
(i.e., pre-existing ADA) that was boosted to a 4-fold or higher level 
following drug administration. 
For this group of subjects, the fold increase in titer (ratio of peak 
post-administration titer to baseline titer) and range of titer 
increases (median, IQR) will be presented. 
The combination of both treatment-induced and treatment-boosted ADA 
(i.e., the percentage of patients fulfilling this criterion) is defined as 
ADA incidence. 
• nAb positive at any visit (including baseline and all post-baseline 
measurements). 
All immunogenicity data will be listed. 
 
Only if immunogenicity data will allow (i.e., if the number of ADA+ subjects will be 
≥3), the effect of immunogenicity on PK and safety will be evaluated: 
• PK: Serum concentration/time curves will be presented in linear/linear and 
log/linear scale. Plots will be presented by dose level and subject ADA status 
(i.e., ADA+ or ADA-), based on arithmetic means; 
• Safety: The number and percentage of patients with treatment-emergent AEs 
will be summarized by subject ADA status (i.e., ADA+ or ADA-), in line with 
the summary reported in Section 3.1.3. 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 21 of 65 
3. 
SAFETY ANALYSES 
3.1 
ADVERSE EVENTS 
3.1.1 
Available data 
Adverse events (AEs) are coded into system organ classes and preferred terms using 
the medical dictionary for regulatory activities (MedDRA, see section 10.3). For each 
AE, start and stop date(time)s are collected as well as intensity, a seriousness flag, 
seriousness criteria, treatment-relationship, action taken towards the study treatment 
and outcome. 
Immediate hypersensitivity reactions (IHRs) are collected in a dedicated eCRF and 
are coded according to MedDRA dictionary (see section 10.3). For each IHR, start 
and stop date(time)s are collected as well as associated signs/symptoms, severity and 
suspected anaphylaxis. 
3.1.2 
Derivation rules 
Pre-treatment AEs are defined as AEs starting between date of informed consent with 
00:00 added as time part and the date(time) of first study treatment administration – 1 
minute, extremes included. 
Treatment-emergent adverse events (TEAE) are defined as AEs starting on or after 
first administration of any study treatment. 
Adverse drug reactions (ADRs) are defined as TEAEs related to study treatment or 
with missing relationship. 
Based on their start date(time), AEs will be allocated to the phase during which they 
started. Phases are defined in section 6.2.1. In case the AE start date(time) is 
incomplete or missing and the AE could consequently be allocated to more than one 
phase, a worst-case allocation will be done as detailed below: 
• Treatment phase vs. non-treatment phase: AE will be allocated to the 
treatment phase. 
A fatal AE is defined as an AE with outcome ‘fatal’. 
An AE for which the study treatment was discontinued is defined as an AE with 
action taken ‘drug permanently withdrawn’. 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 22 of 65 
AE onset and duration will be calculated as follows: 
• AE onset day (vs. first administration) = 
o AE start date < date of first administration: AE start date – date of 
first administration 
o AE start date ≥ date of first administration: AE start date – date of 
first administration + 1 day 
• AE duration (rounded as detailed in section 6.3.4) = 
o If start and stop date(time)s are available: 
- 
AE end date(time) – AE start date(time) + 1 minute 
Note: If AE duration is less than 1 hour, the duration will be presented in 
minutes. If the AE duration is 1 hour or more, but less than 1 day, it will be 
presented in hours. If AE duration is 1 day or more, it will be presented in 
days. 
o If only start and stop dates are available: 
- 
AE end date – AE start date + 1 day 
- 
date of last contact – AE start date + 1 day (when the AE start 
date is fully known but the AE is not resolved at the end of 
the study); in this case the duration will be presented as “>x 
days”. 
3.1.3 
Presentation of results 
Tables will present TEAEs and IHRs only. Pre-treatment AEs will only be listed. 
An overview table will show the number and percentage of subjects with at least one 
event and the number of events by treatment for the following: 
• TEAEs 
• Serious TEAEs 
• Non-serious TEAEs 
• ADRs 
• Serious ADRs 
• Grade 3 or 4 TEAEs 
• TEAEs leading to study treatment discontinuation 
• TEAEs leading to death 
• Immediate hypersensitivity reactions 
Separate summary tables by MedDRA system organ class and preferred term will 
show the number and percentage of subjects with at least one event and the number of 
events by treatment for the aforementioned categories (except for IHRs). Each AE 
record in the clinical database is considered as a distinct adverse event and is counted 
as such. Blank system organ classes and preferred terms, if any, will be shown as 
‘Not Available’ in the tables and listings. 
All AEs, including pre-treatment events and all coding information will be listed. All 
IHR, including all reaction details will be listed. Separate listings will be prepared for 
the categories presented in the summary tables. 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 23 of 65 
3.2 
CLINICAL LABORATORY EVALUATION 
3.2.1 
Available data 
Per protocol, the following safety laboratory parameters are expected to be collected 
at Screening, at Day 1 pre-dose, at Day 2, 7, 14, 28, 56 and 84: 
• Biochemistry: creatinine, urea, aspartate aminotransferase, alanine 
aminotransferase, gamma-glutamyl transpeptidase, total bilirubin, 
alkaline phosphatase, sodium, potassium, chlorine, and fasting glucose. 
• Haematology: red blood cells count, white blood cells count and 
differential (neutrophils, eosinophils, lymphocytes, monocytes, 
basophils; % and values), total haemoglobin, haematocrit, and platelets 
count. 
• Urinalysis (at Screening only): quantitative (proteins) and urinalysis – 
qualitative (ketones, microscopic examination of the sediment), will 
only be listed. 
• Serum and urine pregnancy test and FSH (at Screening, Day 1, Day 28, 
Day 56, and Day 84 only), will only be listed. 
Normal ranges are available as provided by the laboratory. 
3.2.2 
Derivation rules 
Since not all the clinical sites involved in the study are able to provide WBC 
differential results but rather WBC absolute count results only, the WBC differential 
values at the given timepoint/assessment will be derived according to the following 
formula: 
𝑊𝐵𝐶 𝑡𝑦𝑝𝑒 𝑑𝑖𝑓𝑓𝑒𝑟𝑒𝑛𝑡𝑖𝑎𝑙 (%) = (𝑊𝐵𝐶 𝑡𝑦𝑝𝑒 (𝑐𝑜𝑢𝑛𝑡)
𝑊𝐵𝐶 𝑡𝑜𝑡𝑎𝑙 (𝑐𝑜𝑢𝑛𝑡)) ∗100 
 
where WBC types are: neutrophils, eosinophils, lymphocytes, monocytes and 
basophils. 
Derived differential values will be used for analysis purposes, while observed 
differential values (when available) will be listed only. 
The following abnormality categories will be defined: 
• Low: value < lower limit of normal range; 
• Normal: lower limit of normal range ≤ value ≤ upper limit of normal 
range; 
• High: value > upper limit of normal range. 
Notes: 
• No normal ranges will be available for the derived WBC type 
differentials. 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 24 of 65 
• Classification will be done in standardised units, by using non-imputed 
values and limits as reported in standardized units in the clinical 
database: a value <X where X equals the lower limit of normal range 
will be classified as low. A value X with normal range <X will be 
classified as high. 
• If not straightforward how to categorize results, e.g. when results are 
reported as ranges, a worst-case approach will be used. A value of ‘4 to 
6’ with normal range ‘0 to 5’ will thus be classified as normal for pre-
dose assessments but as high for post-dose assessments. 
3.2.3 
Presentation of results 
The statistical analysis will present results in standardised units. 
Continuous laboratory parameters (biochemistry and haematology) will be 
summarised by means of descriptive statistics at each analysis visit by treatment. 
Actual values and changes from baseline will be tabulated. Categorical parameters 
will be listed only. 
Laboratory abnormalities will be presented by treatment as cross-tabulations of the 
abnormality at each post-dose analysis visit and at the worst-case analysis visit versus 
the baseline abnormality. 
All laboratory data will be listed. 
3.3 
VITAL SIGNS 
3.3.1 
Available data 
The following vital signs parameters are collected: 
• duplicate systolic (SBP) and diastolic blood pressure (DBP) in supine 
position. 
• pulse rate. 
• respiratory rate. 
• body temperature. 
• oxygen saturation. 
Vital signs (blood pressure, pulse rate, respiratory rate, body temperature): systolic 
and diastolic blood pressure will be evaluated in duplicate after 5 minutes in supine 
position. Vital signs will be measured at the following timepoints: screening, pre-
dose, every 15 minutes during the infusion (e.g., 15, 30, 45, 60, 75, 90, 105, etc.), at 
the end of the infusion and 30 min, 1, 2, 3, 4, 6, 8, and 20 hours after the end of the 
infusion and 5, 7, 14, 28, 56, and 84 days post-dose. 
Oxygen saturation: will be measured at screening and continuous monitoring will 
occur from pre-dose to 10 hours post-dose at the following timepoints: pre-dose, 
every 15 minutes during the infusion (e.g., 15, 30, 45, 60, 75, 90, 105, etc.), at the end 
of the infusion and 30 min, 1, 2, 3, 4, 6, 8, hours after the end of infusion. Oxygen 
saturation will also be measured at 20 hours after the end of infusion, and 5, 7, 14, 28, 
56 and 84 days post-dose and in case of early termination visit. 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 25 of 65 
3.3.2 
Derivation rules 
Mean values of the duplicates will be calculated per time point and rounded as 
detailed in section 6.3.4. Records belonging to the same duplicate will be identified 
using variable VSREFID. All records of the duplicate will be used to calculate the 
mean, even if less or more than the expected two. The date and time of the first 
member of the duplicate will be assigned to this mean value. Throughout the analysis, 
including the derivation of baseline and abnormalities, the mean values will be used. 
Individual duplicate values will only be listed. 
The following change from baseline abnormality categories will be defined: 
• Changes from baseline: 
o Diastolic blood pressure 
- 
Decrease from baseline >10 mmHg 
- 
Increase from baseline >10 mmHg 
o Systolic blood pressure 
- 
Decrease from baseline >20 mmHg 
- 
Increase from baseline >20 mmHg 
3.3.3 
Presentation of results 
Vital signs and oxygen saturation parameters will be summarised by means of 
descriptive statistics at each analysis time point by treatment. Actual values (with 
2-sided 95% CI) and changes from baseline (with 2-sided 95% CI) will be tabulated. 
For the blood pressure parameters, the number and percentage of subjects with 
abnormal changes from baseline will be presented at each post-baseline time point and 
at the worst-case analysis visit by treatment. 
All vital signs data will be listed. 
Graphs of the mean changes from baseline over time will be prepared for the vital signs 
and oxygen saturation parameters by treatment. In addition, individual graphs of the 
changes from baseline over time will be presented by treatment for the vital signs and 
oxygen saturation parameters. 
3.4 
ELECTROCARDIOGRAMS 
3.4.1 
Available data 
The following electrocardiogram (ECG) parameters will be collected: 
• Triplicate local 12-lead ECG at Screening: heart rate (HR), PR interval, 
QRS interval, QT interval, corrected QT interval (Fridericia) (QTcF) 
and the corresponding interpretation 
• Local 12-lead single ECG at other visits: heart rate (HR), PR interval, 
QRS interval, QT interval, corrected QT interval (Fridericia) (QTcF) 
and the corresponding interpretation 
ECGs will be performed at Screening visit, at pre-dose on Day 1, and Days 2, 7, 28, 
and 84 days post-dose and in case of early termination visit. 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 26 of 65 
3.4.2 
Derivation rules 
Mean values of the triplicates will be calculated at Screening and rounded as detailed 
in section 6.3.4. Records belonging to the same triplicate will be identified using 
variable EGREFID. All records of the triplicate will be used to calculate the mean, 
even if less or more than the expected three. Throughout the analysis, including the 
derivation of baseline and abnormalities, the mean values will be used. Individual 
triplicate values will only be listed. 
For QTcF interval (ms), the following abnormality categories are defined: 
• Actual values: 
o Males: 
- 
> 450 ms 
- 
> 480 ms 
- 
> 500 ms 
o Females: 
- 
> 470 ms 
- 
> 500 ms 
• Changes from baseline: 
o Increase from baseline >30 ms 
o Increase from baseline >60 ms 
Note: The worst-case, as defined in section 6.2.5, is the highest value and associated 
change. 
3.4.3 
Presentation of results 
Local safety 12-lead ECG parameters (HR, PR, QRS and QTcF) will be summarised 
by means of descriptive statistics at each analysis time point by treatment. Actual 
values (with their 95% CI) and changes from baseline (with their 90% CI) will be 
tabulated. 
For QTcF, the number and percentage of subjects with abnormal actual values will be 
presented at each post-dose time point and at the worst-case post-baseline analysis 
visit by treatment. 
For QTcF, the number and percentage of subjects with abnormal changes from 
baseline will be presented at each post-dose time point and at the worst-case analysis 
visit by treatment. 
All ECG data will be listed. 
Graphs of the mean changes from baseline over time will be prepared for the 
continuous ECG parameters by treatment. In addition, individual graphs of the 
changes from baseline over time will be presented by treatment. 
3.5 
LUNG FUNCTION 
3.5.1 
Available data 
The following lung function parameters are collected: 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 27 of 65 
• Spirometry: Forced Expiratory volume in 1 second (FEV1), predicted FEV1, 
percent predicted FEV1, forced vital capacity (FVC), predicted FVC, percent 
predicted FVC and FEV1/FVC ratio. 
Spirometry will be assessed at the following timepoints: screening, 7, 28, 56, 
and 84 days post-dose and in case of early termination visit. 
• Diffusing capacity: DLCO [unadjusted], DLCO % predicted, DLCO corrected for 
haemoglobin, DLCO corrected for haemoglobin % predicted, carbon monoxide 
transfer coefficient [KCO], and alveolar volume [VA]. 
Diffusing capacity will be assessed at the following timepoints: screening, 28, 
56, and 84 days post-dose and in case of early termination visit. 
3.5.2 
Presentation of results 
Spirometry: 
Spirometry parameters will be summarised by means of descriptive statistics (with 
their 95% CI) at each analysis time point by treatment. Actual values, changes from 
baseline and relative changes from baseline will be tabulated. 
Graphs of the absolute and relative mean changes from baseline over time will be 
prepared by treatment. 
All spirometry parameters will be listed. 
Diffusing capacity: 
Diffusing capacity parameters will be summarised by means of descriptive statistics 
(with their 95% CI) at each analysis time point by treatment. Actual values, changes 
from baseline and relative changes from baseline will be tabulated. 
Graphs of the absolute mean changes from baseline over time will be prepared by 
treatment for DLCO % predicted and DLCO corrected for haemoglobin. 
All diffusing capacity parameters will be listed. 
3.6 
SYSTEMIC MARKERS FOR EVALUATION OF IMMEDIATE 
HYPERSENSITIVITY REACTIONS 
3.6.1 
Available data 
Following systemic markers for evaluation of immediate hypersensitivity reactions 
will be collected: Cytokine markers (IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-
10, IL-12 (p70), and IL-13), mast cell tryptase, complement markers (C3a, C5a, 
CH50, and SC5b-9), and CHF10067 IgE. 
3.6.2 
Presentation of results 
The statistical analysis will present results in standardised units. 
Systemic markers will be summarised by means of descriptive statistics, if data is 
available for at least 3 subjects, at each timepoint by treatment. Actual values and 
changes from baseline will be tabulated. 
3.7 
PHYSICAL EXAMINATIONS 
Abnormal physical examination findings will be listed. 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 28 of 65 
4. 
OTHER VARIABLES 
4.1 
TG2 IN PLASMA 
According to the protocol, the exploratory endpoint of this study is: 
• TG2 levels in plasma 
4.1.1 
Available data 
TG2 levels in plasma samples be collected pre-dose and on Days 14, 28, 56, and 84. 
4.1.2 
Presentation of results 
The statistical analysis will present results in standardised units. 
TG2 levels in plasma will be summarised by means of descriptive statistics at each 
analysis visit by treatment. Actual values (with their 95% CI) and changes from 
baseline (with their 95% CI) will be tabulated. 
Graphs of the mean changes from baseline over time will be prepared by treatment. In 
addition, individual graphs of the changes from baseline over time will be presented 
by treatment and ADA positivity/negativity (see definitions in Section 2.2.2). 
 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 29 of 65 
5. 
GENERAL CHARACTERISTICS ANALYSES 
5.1 
SUBJECT DISPOSITION 
The following subject data will be tabulated by treatment and overall: 
• The number of screen failures 
• The number and percentage of subjects who completed or discontinued 
the study as documented on the study termination page and the number 
and percentage of subjects for each study discontinuation reason 
• The number of subjects in each analysis set 
• The number and percentage of subjects for each analysis visit 
All information collected in the eCRF concerning allocation, code breaking, study 
discontinuation and information on phases, dates of first signed informed consent, last 
visit and last contact (over the whole study) will be listed. 
5.2 
IMPORTANT PROTOCOL DEVIATIONS AND ELIGIBILITY 
The number and percentage of subjects with important protocol deviations, per 
category and type, will be tabulated, by treatment and overall. 
All available information concerning important protocol deviations violations on 
eligibility criteria (only violated eligibility criteria having DV.DVCAT = 
'INCLUSION/EXCLUSION CRITERIA') and restrictions will be listed. 
5.3 
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS 
5.3.1 
Available data 
The following parameters will be available: 
• Demographics: women of childbearing potential (yes / no / 
post-menopausal), age, sex, race, BMI, height and weight at screening, 
date of birth, and date of signing informed consent form (ICF), smoking 
status, duration and number of pack-years 
• Screening tests: serology (Human Immunodeficiency Virus Antibody 
(Ab-HIV1 and 2), Hepatitis B surface Antigen (HBsAg), Hepatitis B 
core antibody (anti-HBc), immunoglobulin M Hepatitis B core antibody 
(IgM anti-HBc), Hepatitis C Virus Antibody (Ab-HCV)) and Hepatitis 
C Virus RNA PCR, ethanol and urine drug screen (cannabinoids, 
opiates, cocaine, benzodiazepine, amphetamines and barbiturates) and 
cotinine test 
• Baseline disease characteristics: date of diagnosis, type of diagnosis 
(usual interstitial pneumonia (UIP) pattern, possible UIP pattern, 
probable UIP pattern), IPF diagnosis confirmation, biopsy, antifibrotic 
treatment for IPF (Nintedanib or Pirfenidone), SoC treatment 
(Nintedanib or Pirfenidone) well tolerated, exacerbation history (number 
of exacerbations in the 3 months before screening and end date of the 
most recent exacerbation) 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 30 of 65 
5.3.2 
Derivation rules 
The following parameters will be derived: 
• Age categories: 
o >=40 and <65 years 
o >=65 and <85 years 
o >=85 years 
• Time since diagnosis (years): (date of ICF – date of diagnosis)/365.25 
Note: Partially missing dates will be imputed as specified in section 6.3.2 
• Time since most recent exacerbation (months): (date of ICF – date of 
last documented acute exacerbation)/30.4375 
Note: Partially missing dates will be imputed as specified in section 6.3.2 
5.3.3 
Presentation of results 
Demographics will be presented by treatment and overall using descriptive statistics 
for age, height, weight, BMI, smoking duration and number of pack-years (current 
and ex-smokers only) and frequency tabulations for sex, race, age category and 
smoking status (tobacco and/or e-cigarettes). 
Baseline disease characteristics will be presented by treatment and overall using 
descriptive statistics for continuous parameters and frequency tabulations for 
categorical parameters. 
All demographic data, baseline disease characteristics and screening tests will be 
listed. 
5.4 
MEDICAL HISTORY AND CONCOMITANT DISEASES 
5.4.1 
Available data 
Medical history and concomitant diseases findings are coded using the medical 
dictionary for regulatory activities (MedDRA, see section 10.3) into system organ 
classes and preferred terms. For each finding (MH.MHCAT is ‘GENERAL 
MEDICAL HISTORY’), a start and stop date or ongoing flag is collected. 
5.4.2 
Derivation rules 
The following selection will be performed: 
• Medical history finding: not ongoing at informed consent 
(MH.MHENRTPT is ‘BEFORE’) 
• Concomitant disease finding: still ongoing at informed consent 
(MH.MHENRTPT is ‘ONGOING’ or missing) 
5.4.3 
Presentation of results 
Medical history and concomitant diseases will be tabulated separately by treatment 
and overall. Each table will show: 
• The number and percentage of subjects with findings 
• The number and percentage of subjects with findings by system organ 
class and preferred term 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 31 of 65 
All medical history and concomitant diseases data will be listed separately. 
5.5 
PROCEDURES AND MEDICATIONS 
5.5.1 
Available data 
All procedures are coded into system organ classes and preferred terms using the 
medical dictionary for regulatory activities (MedDRA, see section 10.3). For each 
procedure, start and stop dates or ongoing flag are collected. 
All medications are coded using WHODrug (see section 10.3). ATC coding up to 
level 5 is available in the clinical database. For each medication, a start date(time) or 
prior flag and stop date(time) or ongoing flag are collected. 
5.5.2 
Derivation rules 
Based on their start and stop date(time), procedures and medications will be allocated 
to each phase during which they were performed/administered. A 
procedure/medication can therefore be reported in more than one phase. 
Phases are defined in section 6.2.1. Procedures/medications with (partially) missing 
date(time)s will be allocated to each phase unless the available parts of the 
procedure/medication start or stop date(time) provide evidence that the 
procedure/medication was not performed/taken during that phase. 
Based on their start and stop date(time) procedures and medications will be allocated 
to one of the following categories: 
• Prior: the procedure/medication stopped prior to first study treatment 
administration 
• Maintained: the procedure/medication started before first study 
treatment administration and was ongoing at first study treatment 
administration 
• Concomitant: the procedure/medication started at or after first study 
treatment administration 
For procedures/medications with (partially) missing date(time)s not allowing 
allocation to one unique category, a worst-case allocation will be done based on the 
available parts of the medication/procedure start or stop date(time). The 
medication/procedure will be allocated to the first category allowed by the available 
data, according to the following order: 
• Concomitant 
• Maintained 
• Prior 
Note: these procedures/medications will only be allocated to the phases that match the 
worst-case allocated category. 
5.5.3 
Presentation of results 
Procedures: 
The number and percentage of subjects with procedures and the number and 
percentage of subjects with procedures by system organ class and preferred term 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 32 of 65 
alphabetically sorted will be tabulated per category (prior, maintained, and 
concomitant); by treatment and overall. Blank system organ classes and preferred 
terms, if any, will be shown as ‘Not Available’ in the tables. 
Subjects having more than one procedure allocated to the same category within the 
same treatment, system organ class and preferred term will be counted only once. 
All procedures data will be listed. 
Medications: 
The number and percentage of subjects with medications and the number and 
percentage of subjects with medications by anatomical main group (level 1), 
therapeutic subgroup (level 2), chemical subgroup (level 4), and preferred name will 
be tabulated per category (prior, maintained, and concomitant); by treatment and 
overall. Blank ATC levels and preferred names, if any, will be shown as ‘Not 
Available’ in the tables. 
Subjects having more than one medication allocated to the same category within the 
same treatment, anatomical main group, therapeutic subgroup, chemical subgroup, 
and preferred name will be counted only once. 
All medications data will be listed. 
5.6 
EXPOSURE TO STUDY TREATMENT 
5.6.1 
Available data 
For each study treatment administration, the start and end date(time)s, kit number, the 
dose, the infusion rate, the reason for interruption or rate change and the action taken 
during the infusion will be recorded. 
5.6.2 
Presentation of results 
All exposure data will be listed. 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 33 of 65 
6. 
GENERAL METHODOLOGY 
6.1 
ANALYSIS SETS 
6.1.1 
Analysis sets 
The following analysis sets will be considered in the statistical analysis: 
Enrolled Set (ENR): 
subjects who signed an informed consent to participate 
in this study 
Randomised Set (RND): 
subjects who were randomised into this study 
Safety Set (SAF): 
all randomised subjects who receive a dose of study 
treatment, including partial dose 
PK Set: 
all subjects from the safety set excluding subjects 
without any valid PK measurement or with important 
protocol deviations significantly affecting PK, for 
example, use of non-permitted medications.  
Notes: 
• Having signed an informed consent is defined as having a complete 
informed consent signature date in the database. 
• Randomised is defined as having a randomisation date in the database or 
any information to confirm randomisation. 
• Having received at least one dose of study treatment is defined as 
having an exposure date or any information confirming exposure. 
• Exact definition of important protocol deviations significantly affecting 
PK evaluations will be discussed by the Chiesi team during the Data 
Review Meeting (DRM) and described in the DRR and/or PK DRR. The 
PK set will be defined in the DRR and/or PK DRR. See section 6.1.3.1 
for further details. Subjects will not be excluded on the basis of 
statistical analysis or for PK reasons, except in the cases defined in the 
European Medicine Agency guideline on the Investigation of 
Bioequivalence 
Unless stated otherwise, the SAF will be used for the general characteristics, 
demographics and baseline characteristics, immunogenicity and safety tables and 
figures and the RND will be used for the general characteristics and safety listings. In 
addition, the PK set will be used for demographics and baseline characteristics tables, 
if different than the SAF. PK set will be used for the PK tables, listings and figures. 
6.1.2 
As planned versus as actual analysis 
For the safety, immunogenicity, other variables (TG2) and PK analyses the actual 
treatment of the subject will be considered. The general characteristics analyses will 
be by planned treatment. In the listings the actual treatment will be presented. 
6.1.3 
Exclusion of data from the statistical analyses 
The important/non-important protocol deviation definitions are defined in the 
Protocol Deviation Criteria List and will be used to identify cases that will be 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 34 of 65 
discussed by Chiesi during the DRM. Decisions on whether subjects are to be 
excluded from the analysis set and/or values are to be excluded from the analysis will 
be fully documented in the DRR and/or PK DRR. 
In case of important protocol deviations impacting specific time points, only the 
affected data at the specific time point will be excluded from the applicable analysis 
sets. These cases will be documented in the DRR and/or PK DRR. 
6.1.3.1 
EXCLUSION OF DATA FROM PK ANALYSIS 
Subjects and/or PK data can be excluded from the PK set or PK analysis based on the 
important protocol deviations with potential impact on PK. Below, the rules for 
handling PK assessments not performed, or performed out of the allowed window, or 
not reportable are described. In addition to the important protocol deviations, PK data 
can be excluded based on specific rules after disclosure of the bioanalytical data or 
specific criteria for PK parameters. The criteria of the latter are described in section 
2.1.2. 
Important protocol deviations 
The impact of PK assessments not performed, or performed out of the allowed 
window, or not reportable will depend on the number of deviations per profile and the 
timing of the deviation:  
At predose 
The impact of serum PK assessments performed out of allowed window or taken after 
start of infusion will be evaluated during the DRM. 
For serum PK assessments not performed or not reportable at pre-dose, see section 
6.3.1 for proper imputation rules for PK parameter estimation. 
At tmax 
For serum PK assessments not performed, or performed out of allowed window, or 
not reportable at the expected tmax, the general rule is the following: the resulting 
estimation of Cmax, tmax and AUCs could not be accurately determined, and these 
parameters will be excluded from PK analyses. This deviation will have no impact on 
the estimation of t1/2. The expected tmax of CHF10067 is within 1 hour from the end of 
infusion.  
At tinf 
For serum PK assessments not performed, or performed out of allowed window, or 
not reportable at the expected tinf, the general rule is the following: the resulting 
estimation of Cinf could not be accurately determined, and this parameters will be 
excluded from PK analyses. This deviation will have no impact on the estimation of 
t1/2.  
At last planned sampling time point 
For serum PK assessments performed out of allowed window at the last planned 
sampling time point, in order to minimise the risk to under- or overestimate AUC0-t, 
AUC0-t will be calculated using the theoretical time of the last planned timepoint 
instead of the actual time. Note that in case the last sample is taken before the planned 
sampling time point, this AUC0-t can only be estimated if λz is reliably measurable.  




Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 36 of 65 
Subjects with Day 1 pre-dose values exceeding 5% of the Cmax will be excluded from 
the PK set.  
AUC0-t lower than 5% of the corresponding geometric mean AUC0-t 
Subjects with an AUC0-t lower than 5% of the corresponding geometric mean AUC0-t 
(calculated without inclusion of data from the outlying subject) will be excluded from 
the PK set. 
Abnormal PK concentrations or profiles 
Abnormal PK concentrations or profiles will be discussed case by case in the PK 
DRR. 
6.1.3.2 
EXCLUSION OF DATA FROM SAFETY ANALYSIS 
Not applicable 
6.2 
PHASES AND TIME POINTS 
6.2.1 
Phases 
Adverse events, medications, and procedures will be allocated to phases. All other 
analyses will not be allocated to phases. Instead, the visit and time point labels 
indicated on the subject’s electronic case report form (eCRF) will be used to allocate 
the assessments. Early termination assessments will be allocated to the treatment 
phase. 
Adverse events and medications: 
Phase 
Start 
End 
Screening 
Date of signing the ICF, with 
00:00 added as time part 
First administration date(time) – 
1 minute 
Treatment 
First administration date(time) 
Date of last contact, with 23:59 
added as time part 
Per definition, and for each subject, the first phase starts on the date of the earliest 
available ICF signature, with 00:00 added as time part. The last available phase ends 
on the date of last contact, with 23:59 added as time part. 
Procedures: 
Phase 
Start 
End 
Screening 
Date of signing the ICF 
First administration date – 1 day 
Treatment 
First administration date 
Date of last contact 
Per definition, and for each subject, the first phase starts on the date of the earliest 
available ICF signature. The last available phase ends on the date of last contact. 
AEs, medications, and procedures will be allocated to phases as described in sections 
3.1.2 and 5.5.2 respectively. 
All PK records (PK concentrations and PK parameters) and IHRs will be allocated to 
the treatment phase. 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 37 of 65 
6.2.2 
Baseline and change from baseline 
The baseline value is the last non-missing value, including unscheduled assessments, 
before the administration of the study treatment. In case this results in more than one 
record with the same date and time, the unscheduled record is selected as baseline. 
Note: decisions on whether a different baseline should be used in the analysis will be 
fully documented in the DRR. 
Change from baseline is defined as: 
Change from baseline at time point t = value at time point t – baseline value. 
Relative change from baseline at time point t is defined as follows: 
• When baseline value is not zero: 100*((value at time point t – baseline 
value) / baseline value) 
• When both baseline value and value at time point t are zero: not 
calculated 
• When baseline value is zero and value at time point t is not zero: not 
calculated 
6.2.3 
Relative day 
Relative days (DY) will be calculated according to the following rule: 
• Concerned date < reference date: DY = concerned date – reference date 
• Concerned date ≥ reference date: DY = concerned date – reference date 
+ 1 
The reference date is the date of administration of study treatment. 
6.2.4 
Analysis visits 
The analysis will use the visits indicated on the subject’s eCRF, while for the time 
points related to the PK concentration data and the vital signs and oxygen saturation 
assessments a windowing approach will be used (see time window definitions below). 
For PK parameter calculation the actual sampling time will be considered, as reported 
in section 2.1.2. 
The screening value is the last available and non-missing value before Day 1. This 
value corresponds to the screening visit, except in case of retesting. Reason for this 
approach is the use of retest results for subject eligibility assessment. 
Unscheduled assessments will not be used in the analysis unless it is selected as 
screening value, or per time window definitions below.  
The unscheduled assessments will be checked during the data review meeting before 
database lock, and any different approach to the rule defined above will be 
documented in the data review report. 
Baseline is defined in section 6.2.2. 
All scheduled and unscheduled assessments will be listed. 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 38 of 65 
Except when defined by time windows, the analysis visit labels will be assigned using 
the following rules: 
• All planned screening, re-screening, eligibility recheck, etc. visits 
occurred during the screening phase will be presented as ‘Screening’. 
• All planned visits occurred during a scheduled day, will be presented as 
‘Day x’ (x = study day, e.g. ‘Day -1’, ‘Day 1’, etc.) 
• Early termination visits will be presented as ‘Early Termination’ 
• Unscheduled visits will be presented as ‘Unscheduled’ unless the 
decision to reallocate the visit is fully documented in the DRR. In case 
of reallocation, the unscheduled visit will be presented with the same 
label as the replaced planned visit (see rules above) 
• Other visits not covered by the rules above will be presented using 
similar labels to the ones used in SDTM (XX.VISIT) 
For PK data, AVISIT(N) will be assigned per PK profile of interest and will be based 
on the eCRF visit of the corresponding study treatment administration. 
The analysis time point labels for pharmacokinetic concentration data, vital signs and 
oxygen saturation, will be assigned using the following time windowing rules. 
Next to the screening value, all assessments, including unscheduled assessments, will 
be allocated to analysis windows. Tables will present the analysis windows as defined 
below and listings will present the analysis windows, as well as the eCRF visits. 
Allocation of assessments will be done according to the following tables: 
Pharmacokinetics: 
 
Analysis time point 
window 
Target time after 
end of infusion 
(hours) 
Time interval (hours) 
Pre-dose 
<0 
Last day 1, pre-dose 
assessment 
EOI 
0 
[0 min;10 min=0.1667] 
2h 
2 
[11min=0.1833;3] 
4h 
4 
[3.0167;6] 
8h 
8 
[6.0167;14] 
20h 
20 
[14.0167;58] 
Day 5 
96 
[58.0167;120] 
Day 7 
144 
[120.0167;228] 
Day 14 
312 
[228.0167; 480] 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 39 of 65 
Day 28 
648 
[480.0167;984] 
Day 56 
1320 
[984.0167;1656] 
Day 84 
1992 
[1656.0167;∞) 
 
Vital signs and oxygen saturation: 
Before and during infusion: 
 
Analysis time point 
window 
Target time vs. 
start of infusion 
(minutes) 
Time interval 
(minutes) 
Pre-dose 
<0 
Last day 1, pre-
dose assessment 
0.25h 
15 
[1;22] 
0.5h 
30 
[23;37] 
0.75h 
45 
[38;52] 
1h 
60 
[53;67] 
1.25h 
75 
[68;82] 
1.5h 
90 
[83;97] 
1.75h 
105 
[98;112] 
2h 
120 
[113;127] 
2.25h 
135 
[128;142] 
2.5h 
150 
[143;157] 
2.75h 
165 
[158;172] 
3h 
180 
[173;187] 
3.25h 
195 
[188;202] 
3.5h 
210 
[203;217] 
3.75h 
225 
[218;232] 
4h 
240 
[233;247] 
4.25h 
255 
[248;262] 
4.5h 
270 
[263;277] 
4.75h 
285 
[278;292] 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 40 of 65 
5h 
300 
[293; 307] 
5.25h 
315 
[308; 322] 
5.5h 
330 
[323; end of 
infusion] 
 
After infusion: 
 
Analysis time point 
window 
Target time vs. 
end of infusion 
(minutes) 
Time interval 
(minutes) 
0h 
0 
[End of infusion; 5] 
0.5h 
30 
[6;45] 
1h 
60 
[46;90] 
2h 
120 
[91;150] 
3h 
180 
[151;210] 
4h 
240 
[211;300] 
6h 
360 
[301;420] 
8h 
480 
[421;840] 
20h 
1200 
[841;1560) 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 41 of 65 
 
Systemic markers: 
 
Analysis time point 
window 
Target time vs. 
end of infusion 
(pre-dose) or 
start of 
hypersensitivity 
reaction (post-
dose) (minutes) 
Time interval 
(minutes) 
Pre-dose 
<0 
Last day 1, pre-
dose assessment 
1h 
60 
[1;90] 
2h 
120 
[91;∞) 
 
Per parameter and analysis window, the value closest to the target time will be used in 
analysis tables and figures, other values will only be listed. If more than one value is 
located at the same distance from the target, then the latest in time will be selected. 
The value latest in time will be identified using, in order of preference, the assessment 
time, the visit and time point label or the group identifier. Missing values are 
removed before the selection is made. 
Partially missing assessment dates or times disabling allocation to analysis windows 
will not be imputed and thus these assessments will not be considered in the per-time 
point analysis, except for the derivation of the worst. 
6.2.5 
Worst-case 
A worst-case analysis visit (presented in the analysis as ‘At Any Time Point’, or 
similar) will be created for parameters for which abnormalities are defined to 
summarise values considered as the worst-case. 
The worst-case analysis visit will be derived within the treatment phase, including 
scheduled and unscheduled assessments as well as the early termination visit 
assessments. Only post-baseline assessments will be considered for the worst-case 
analysis visit. 
6.3 
IMPUTATION AND ROUNDING RULES 
6.3.1 
Missing values 
No imputation of missing values will be done (i.e., observed cases analysis), except 
missing pre-dose concentrations will be imputed per rules below for PK parameter 
derivation only: 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 42 of 65 
• The missing pre-dose PK concentration will be set to 0 for PK 
parameter derivation. 
6.3.2 
Handling partially or completely missing dates in 
calculations 
Partially missing date of date of diagnosis or end date of the most recent exacerbation 
will be imputed as follows for the calculation of time since event: 
• Missing day will be imputed with 1 
• Missing day and month will be imputed with 1JAN 
6.3.3 
Values below or above a threshold 
Safety values expressed as below (or above) the limit of quantification will be 
imputed by the value of the quantification limit itself. Listings will always show the 
non-imputed values. 
PK concentrations below the quantification limit will be flagged as BLQ in the 
concentration and parameters tables. All BLQ values will be considered as 0.00 for 
PK and descriptive statistical analyses.  
6.3.4 
Rounding of derived variables 
Derived variables will be rounded at display level: 
• AE duration will be presented with 1 decimal. 
• Mean of duplicates/triplicates will be rounded to the nearest integer. 
Note: since the rounding is applied at display level, in the listings, the 
change from baseline could be slightly different to the listed value at 
time point t – baseline value 
• Relative change from baseline will be presented with 1 decimal. 
• Time since diagnosis, last exacerbation will be presented with 1 
decimal. 
• Derived laboratory differential values will be presented with 1 decimal. 
• Log-transformed values will not be rounded. 
• PK concentrations and parameters (as well as descriptive statistics) will 
be presented in tables with 3 significant digits except values >1000, 
which will be presented without decimals and tmax which will be 
presented with 2 decimals. 
6.3.5 
Outliers 
Potential outliers will be discussed during the review of the data by the Chiesi team. 
Decisions on whether values are to be excluded from the analysis will be fully 
documented in the DRR and/or PK DRR. 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 43 of 65 
6.4 
PRESENTATION OF RESULTS 
6.4.1 
Calculation of descriptive statistics and percentages 
For continuous parameters, full descriptive statistics will only be presented if there 
are at least 2 non-missing observations. Alternatively, only the number of non-
missing data points and mean are shown. 
Descriptive statistics of non-PK data will include the number of non-missing data 
points, the arithmetic mean, the standard deviation (SD), the median, minimum and 
maximum. 
Descriptive statistics of safety parameters will additionally include 95% (or 90%) 
confidence interval (CI) on the mean (based on t-distribution, without continuity 
correction). 
Mean, median, SD and CI will be presented with one more decimal place than the 
individual values, with a maximum of 4 decimal places. Minimum and maximum will 
be presented with the same number of decimal places as the individual values, with a 
maximum of 3 decimal places. 
Descriptive statistics of PK concentrations will include the number of non-missing 
data points, the arithmetic mean, SD, the median, minimum and maximum and the 
coefficient of variation (CV) % of arithmetic mean. If more than half of values are 
BLQ at a specific timepoint, then SD and CV% will not be calculated and reported as 
“NC” (not calculated) in the tables.  
Descriptive statistics on PK parameters will additionally include geometric mean and 
geometric CV%, except tmax for which the descriptive statistics will include the 
number of non-missing data points, the median, minimum and maximum.  
The descriptive statistics on PK data will be presented as described in section 6.3.4. 
The slopes and their 90%CI from the power model on PK parameters will be 
presented with two decimals. 
For event-type data, the denominator will be all subjects in the analysis set and phase. 
All treatments will be shown, even if no events are present. 
For frequency tabulations and cross-tabulations, missing values will not be included 
in the denominator count when computing percentages. For cross-tabulations of post-
baseline results versus baseline results, a ‘missing’ category will be shown for 
baseline results if applicable. 
Percentages will be shown with one decimal place. 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 44 of 65 
6.4.2 
Presentation of treatments 
The following treatment labels will be used in the tables, listings and figures: 
• CHF10067 1000 mg 
• CHF10067 2000 mg 
• CHF10067 3000 mg 
• CHF10067 Total + 
• Placebo * 
• Overall # 
+ “CHF10067 Total” is the combination of “CHF10067 1000mg”, “CHF10067 
2000mg” and “CHF10067 3000mg” treatment groups, will be shown for all 
demographics and safety tables (with the exception of disposition, analysis set, 
protocol deviations and PK). 
* All placebo subjects (from all cohorts) will be pooled into one “Placebo” group for 
presentation in tables and figures. 
# Unless specified otherwise, an “Overall” column, to summarise all subjects over 
treatments (including placebo), will be presented only in tables showing data that are 
not affected by the study treatment (i.e., general characteristics analyses). The overall 
column will be shown last. 
6.4.3 
Ordering in tables, listings and figures 
If the treatments are presented as columns, tables will be sorted by analysis visit and 
time point. Otherwise, tables will be sorted first by treatment, then by analysis visit 
and time point. The active treatments will be shown first in ascending dose order, and 
then placebo: CHF10067 1000 mg, CHF10067 2000 mg, CHF10067 3000 mg, 
CHF10067 Total and then placebo. 
All tables and figures will be presented per treatment, unless specified otherwise. 
All listings will be ordered by subject and then by analysis visit and time point 
(chronologically), unless specified otherwise. 
In tables and figures showing several parameters, each parameter will begin on a new 
page and parameters will be sorted alphabetically, within the parameter category if 
applicable. 
6.4.4 
Raw SAS output 
In addition to the statistical output as described in section 9, raw SAS output will be 
delivered in separate files as ‘Appendix to Table 14.x.x.x’ for all tables presenting 
inferential statistics. The layout of the appendices will be similar to the table (study 
identifier, SAS program name, production date, page count); presenting the raw SAS 
output in the body section. 
6.4.5 
eCTD tables 
Additional tables will be delivered in separate files as ‘Appendix to Table 14.x.x.x’ 
for all tables presenting PK parameters: they will be created separately for each 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 45 of 65 
analyte and will present the subjects/profiles (if any), per treatment, showing AUC0-t/ 
AUC0-∞ <0.8, Cmax as the first point and pre-dose sample >5% Cmax per treatment. 
 
 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 46 of 65 
7. 
CHANGES TO THE PLANNED ANALYSIS 
7.1 
CHANGES NOT COVERED BY PROTOCOL AMENDMENTS BEFORE 
UNBLINDING 
• “Immunogenicity Analysis”: Section 2.2 of the SAP to clarify 
section ‘12.3.5.3 Immunogenicity’ of the study protocol. 
Section 2.2 of this SAP, compared to Section 12.3.5.3 of the study 
protocol, provides clear definitions and a corresponding summary table 
on the whole Safety Set for: ADA evaluable subject, ADA positive 
subjects, ADA prevalence, ADA incidence (i.e., treatment-induced and 
treatment-boosted ADA) and nAb positive subject. As a consequence of 
the above update, the two summary tables on the subset of ADA 
positive subjects, initially foreseen in Section 12.3.5.3 of the study 
protocol, have been translated into a listing (see Listing 16.2.6.1 at 
Section 9.2 of the present document). 
 
• “Vital signs”: Section 3.3 of the SAP to clarify section ‘12.3.5.4.3 
Oxygen saturation’ of the study protocol. 
While per protocol, individual time profile plots are not requested for 
oxygen saturation, these will be produced to be in line with the vital 
signs analysis. 
 
• “Lung function”: Section 3.5 of the SAP to clarify section ‘12.3.5.4 
Pulmonary assessments’ of the study protocol. 
The following summary analysis is described in the protocol: 
 
“The frequency of subjects with FEV1% and FVC% below the lower 
limit of normal at each timepoint will be listed and summarised with 
descriptive statistics.” 
 
Since no normal ranges are available for the aforementioned parameters, 
this summary will not be produced. 
 
• “Placebo-corrected change from baseline”: Section 3.4 of SAP to 
clarify Section ‘12.3.5.5 ECG’ of the study protocol. 
Placebo-corrected change from baseline is erroneously mentioned in the 
protocol but it is not applicable for this study design. Therefore, none of 
the analyses related to placebo-related change from baseline will be 
produced. 
 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 47 of 65 
• Section “12.3.6.1 TG2 in plasma” of the study protocol. 
The below text was erroneously included in the study protocol. 
Therefore, the related analyses will not be produced. 
 
“The TG2 levels in plasma obtained from healthy subjects will be 
summarised using descriptive statistics. 
Box-plots summarising the pre-dose levels for treated subjects in the 
study, the healthy subjects’ external group, and each post-dose levels for 
the different doses for treated subjects will be presented.” 
 
• “By dose level”: SAP to clarify Section 12 of the study protocol. 
While across the study protocol ‘dose level’ could be equivalent to 
‘cohort’, and across section 12 of the protocol analyses are defined to be 
performed by ‘dose level’, in the SAP all analyses have been defined as 
‘by treatment’, separating the subjects receiving active study treatment 
and placebo as defined in section 6.4.2 of this SAP. 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 48 of 65 
8. 
REFERENCES 
• ICH Topic E6(R2) Guideline for Good Clinical Practice – Step 5 
(EMA/CHMP/ICH/135/1995), 1 December 2016. 
• ICH guideline E14: the clinical evaluation of QT/QTc interval 
prolongation and proarrhythmic potential for non-antiarrhythmic drugs 
(R3) – questions and answers, January 2016. 
• ICH Topic E9 Statistical Principles for Clinical Trials – Step 5 – Note 
for Guidance on Statistical Principles for Clinical Trials 
(CPMP/ICH/363/96), September 1998. 
• 
D419QC00001-SAP-ed-4_Final Redacted_15Sep21.pdf, available at 
https://clinicaltrials.gov/ct2/show/NCT03043872. 
• El-Khoueiry A. et al, Immunogenicity of durvalumab: analysis of 
pooled pan-tumor data, J Immunother Cancer 2022;10(Suppl 2):A1–
A1603. 
• Shankar G. et al, Assessment and Reporting of the Clinical 
Immunogenicity of Therapeutic Proteins and Peptides—Harmonized 
Terminology and Tactical Recommendations, The AAPS Journal, Vol. 
16, No. 4, July 2014. 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 49 of 65 
9. 
LIST OF TABLES, LISTINGS AND FIGURES 
9.1 
TABLES 
Number 
Title 
Analysis 
Set 
TLFs 
Library 
Template 
Number 
GENERAL CHARACTERISTICS 
14.1.1.1 
Screen Failures (Enrolled Set) 
ENR 
DST001 
 
Tabulation of the reason for screening failures. 
 
 
14.1.1.2 
Disposition by Treatment (Randomised Set) [KFR] 
RND 
DST002 
 
Tabulation of completion/discontinuation and the reason for 
discontinuation. 
 
 
14.1.1.3 
Analysis Sets (Randomised Set) 
RND 
DST005 
 
Tabulation of the number of subjects in each of the analysis sets defined in 
the SAP. 
 
 
14.1.1.4 
Attendance at Study Visits (Randomised Set) 
RND 
SVT001 
 
Tabulation of the number and percentage of subjects per analysis visit. 
 
 
14.1.1.5 
Important Protocol Deviations (Safety Set) 
SAF 
DVT001 
 
Tabulation of the important protocol deviations (at least one), deviation 
category and deviation type by treatment and overall. 
 
 
14.1.1.6 
Important Protocol Deviations Leading to Exclusion from PK Set 
(Safety Set) 
SAF 
DVT001 
 
Tabulation of the important protocol deviations (at least one) leading to 
exclusion from the PK set, deviation category and deviation type by 
treatment and overall. 
 
 
14.1.2.1.1 
Demographic Characteristics (Safety Set) [KFR] 
SAF 
DMT001 
 
Descriptive statistics of continuous parameters and frequency tabulation 
of categorical parameters. 
 
 
14.1.2.1.2 
Demographic Characteristics (PK Set) 
PK 
DMT001 
 
Descriptive statistics of continuous parameters and frequency tabulation 
of categorical parameters. 
 
 
14.1.2.2.1 
IPF History (Safety Set) [KFR] 
SAF 
SCT001 
 
Descriptive statistics of continuous parameters and frequency tabulation 
of categorical parameters. 
Template SCT001 is used, using the IPF parameters instead. 
 
 
14.1.2.2.2 
IPF History (PK Set) 
PK 
SCT001 
 
Descriptive statistics of continuous parameters and frequency tabulation 
of categorical parameters. 
Template SCT001 is used, using the IPF parameters instead. 
 
 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 50 of 65 
Number 
Title 
Analysis 
Set 
TLFs 
Library 
Template 
Number 
14.1.2.3.1 
IPF Exacerbation History (Safety Set) 
SAF 
SCT003 
 
Descriptive statistics of continuous parameters and frequency tabulation 
of categorical parameters. 
Template SCT003 is used, using the IPF exacerbation parameters instead. 
 
 
14.1.2.3.2 
IPF Exacerbation History (PK Set) 
PK 
SCT003 
 
Descriptive statistics of continuous parameters and frequency tabulation 
of categorical parameters. 
Template SCT003 is used, using the IPF exacerbation parameters instead. 
 
 
14.1.2.4 
Smoking Status (Safety Set) 
SAF 
SUT001 
 
Descriptive statistics of continuous parameters and frequency tabulation 
of categorical parameters. 
 
 
14.1.2.5 
Medical History (Safety Set) 
SAF 
MHT001 
 
Tabulation of the number and percentage of subjects with medical history 
findings and number and percentage of subjects with medical history 
findings by system organ class and preferred term. 
 
 
14.1.2.6 
Concomitant Diseases (Safety Set) 
SAF 
MHT001 
 
Tabulation of the number and percentage of subjects with concomitant 
diseases and number and percentage of subjects with concomitant diseases 
by system organ class and preferred term. 
 
 
14.1.2.7 
Prior Procedures (Safety Set) 
SAF 
MHT001 
 
Tabulation of the number and percentage of subjects with prior procedures 
and number and percentage of subjects with prior procedures by system 
organ class and preferred term. 
 
 
14.1.2.8 
Maintained Procedures (Safety Set) 
SAF 
MHT002 
 
Tabulation of the number and percentage of subjects with maintained 
procedures and number and percentage of subjects with maintained 
procedures by system organ class and preferred term. 
 
 
14.1.2.9 
Concomitant Procedures (Safety Set) 
SAF 
MHT002 
 
Tabulation of the number and percentage of subjects with concomitant 
procedures and number and percentage of subjects with concomitant 
procedures by system organ classes and preferred terms. 
 
 
14.1.2.10 
Prior Medications (Safety Set) 
SAF 
CMT001 
 
Tabulation of the number and percentage of subjects with prior 
medications and number and percentage of subjects with medications by 
ATC class (level 1), ATC class (level 2), ATC class (level 4) and 
preferred name. 
 
 
14.1.2.11 
Maintained Medications (Safety Set) 
SAF 
CMT001 
 
Tabulation of the number and percentage of subjects with maintained 
medications and number and percentage of subjects with maintained 
medications by ATC class (level 1), ATC class (level 2), ATC class (level 
4) and preferred name. 
 
 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 51 of 65 
Number 
Title 
Analysis 
Set 
TLFs 
Library 
Template 
Number 
14.1.2.12 
Concomitant Medications (Safety Set) 
SAF 
CMT002 
 
Tabulation of the number and percentage of subjects with concomitant 
medications and number and percentage of subjects with concomitant 
medications by ATC class (level 1), ATC class (level 2), ATC class (level 
4) and preferred name. 
 
 
PHARMACOKINETICS 
14.2.2.1 
Actual Blood Sampling Times for PK Assessments (PK Set) 
PK 
PCT001 
 
Individual actual sampling times of blood samples per dose level 
 
 
14.2.2.2 
CHF10067 Serum Concentrations (ng/mL) by Scheduled Time (PK 
Set) 
PK 
PCT002 
 
Individual values and descriptive statistics of CHF10067 serum 
concentrations per dose level 
 
 
14.2.2.3 
CHF10067 Serum PK Parameters (PK Set) 
PK 
PKT001 
 
Individual values and descriptive statistics of CHF10067 serum PK 
parameters, per dose level 
 
 
14.2.2.4 
Dose Proportionality Assessment of CHF10067 Serum PK Parameters 
(Power Model) (PK Set) 
PK 
 
 
The slope and 90% CI of the power model will be tabulated by PK 
parameter of CHF10067 (AUC0-t, AUCinf, and Cmax) 
 
 
IMMUNOGENICITY 
14.2.4.1 
Summary of ADA Responses (Safety Set) [KFR] 
SAF 
 
 
Tabulation of the number and percentage of subjects as classified in 
section 2.2.3. 
 
 
14.2.4.2 
Summary of TEAEs by Subject ADA Status (Safety Set) 
SAF 
AET001 
 
Tabulation of the number and percentage of subjects with at least one 
TEAE by subject ADA status (ADA+ or ADA-). 
Note: if the number of ADA+ subjects is less than 3, this table will be 
generated without results. Instead, an informative message will be printed 
in this output. 
 
 
SAFETY 
 
ADVERSE EVENTS 
 
14.3.1.1 
Summary of TEAEs (Safety Set) [KFR] 
SAF 
AET001 
 
Tabulation of the number and percentage of subjects with at least one of 
the events described in the SAP. The number of events will also be shown. 
 
 
14.3.1.2 
TEAEs by System Organ Class and Preferred Term (Safety Set) 
SAF 
AET003 
 
Tabulation of the number and percentage of subjects with TEAEs by 
MedDRA system organ class and preferred term. The number of events 
will also be shown. 
 
 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 52 of 65 
Number 
Title 
Analysis 
Set 
TLFs 
Library 
Template 
Number 
14.3.1.3 
Serious TEAEs by System Organ Class and Preferred Term (Safety 
Set) 
SAF 
AET003 
 
Tabulation of the number and percentage of subjects with serious TEAEs 
by MedDRA system organ class and preferred term. The number of events 
will also be shown. 
 
 
14.3.1.4 
Non-Serious TEAEs by System Organ Class and Preferred Term 
(Safety Set) 
SAF 
AET003 
 
Tabulation of the number and percentage of subjects with non-serious 
TEAEs by MedDRA system organ class and preferred term. The number 
of events will also be shown. 
 
 
14.3.1.5 
ADRs by System Organ Class and Preferred Term (Safety Set) [KFR] 
SAF 
AET003 
 
Tabulation of the number and percentage of subjects with ADRs by 
MedDRA system organ class and preferred term. The number of events 
will also be shown. 
 
 
14.3.1.6 
Serious ADRs by System Organ Class and Preferred Term (Safety 
Set) 
SAF 
AET003 
 
Tabulation of the number and percentage of subjects with serious ADRs by 
MedDRA system organ class and preferred term. The number of events 
will also be shown. 
 
 
14.3.1.7 
Grade 3 or 4 TEAEs by System Organ Class and Preferred Term 
(Safety Set) 
SAF 
AET003 
 
Tabulation of the number and percentage of subjects with grade 3 or 4 
TEAEs by MedDRA system organ class and preferred term. The number 
of events will also be shown. 
 
 
14.3.1.8 
TEAEs Leading to Study Treatment Discontinuation by System 
Organ Class and Preferred Term (Safety Set) 
SAF 
AET003 
 
Tabulation of the number and percentage of subjects with TEAEs leading 
to study treatment discontinuation by MedDRA system organ class and 
preferred term. The number of events will also be shown. 
 
 
14.3.1.9 
TEAEs Leading to Death by System Organ Class and Preferred Term 
(Safety Set) 
SAF 
AET003 
 
Tabulation of the number and percentage of subjects with TEAEs leading 
to death by MedDRA system organ class and preferred term. The number 
of events will also be shown. 
 
 
LABORATORY DATA 
 
14.3.2.1 
Haematology: Summary of Actual Values and Changes from Baseline 
(Safety Set) 
SAF 
LBT001 
 
Descriptive statistics of haematology results and changes from baseline by 
treatment, parameter and analysis visit. Table sorted first by parameter, 
then by analysis visit. Each parameter will begin on a new page. 
 
 
14.3.2.2 
Haematology: Shift from Baseline (Safety Set) [KFR] 
SAF 
LBT005 
 
Shift table of the abnormality at each analysis visit versus the baseline 
abnormality per parameter. Each parameter will begin on a new page. 
 
 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 53 of 65 
Number 
Title 
Analysis 
Set 
TLFs 
Library 
Template 
Number 
14.3.2.3 
Biochemistry: Summary of Actual Values and Changes from Baseline 
(Safety Set) 
SAF 
LBT001 
 
Descriptive statistics of biochemistry results and changes from baseline by 
treatment, parameter and analysis visit. Table sorted first by parameter, 
then by analysis visit. Each parameter will begin on a new page. 
 
 
14.3.2.4 
Biochemistry: Shift from Baseline (Safety Set) [KFR] 
SAF 
LBT005 
 
Shift table of the abnormality at each analysis visit versus the baseline 
abnormality per parameter. Each parameter will begin on a new page. 
 
 
VITAL SIGNS 
 
14.3.3.1 
Vital Signs and Oxygen Saturation: Summary of Actual Values and 
Changes from Baseline (Safety Set) 
SAF 
VST001 
 
Descriptive statistics of vital signs and oxygen saturation actual values and 
changes from baseline per parameter and analysis time-point. Table sorted 
by analysis time-point. Each parameter will begin on a new page. 
 
 
14.3.3.2 
Blood Pressure: Summary of Abnormal Changes from Baseline 
(Safety Set) [KFR] 
SAF 
VST004 
 
Tabulation of the blood pressure abnormalities as defined in section 3.3.2 
at each post-baseline analysis time point and at the worst-case analysis 
time point per parameter. Table sorted by analysis time point. Each 
parameter will begin on a new page. Only post-baseline analysis time 
points are shown. 
 
 
ECG 
 
14.3.4.1 
12-Lead ECG: Summary of Actual Values and Changes from Baseline 
(Safety Set) [KFR] 
SAF 
EGT002 
 
Descriptive statistics of continuous 12-lead ECG (HR, PR, QRS, QTcF) 
actual values and changes from baseline per parameter and analysis time 
point. Table sorted by analysis time point. Each parameter will begin on a 
new page. 
 
 
14.3.4.2 
QTcF: Abnormalities (Safety Set) 
SAF 
EGT007 
 
Tabulation of the abnormalities as defined in section 3.4.2 at each post-
dose analysis time point and at the worst-case analysis time-point. Table 
sorted by analysis time point. Only baseline and post-dose analysis time 
points are shown. 
 
 
14.3.4.3 
QTcF: Abnormal Changes from Baseline (Safety Set) [KFR] 
SAF 
EGT008 
 
Tabulation of the QTcF change abnormalities as defined in section 3.4.2 at 
each post-baseline analysis time point and at the worst-case analysis time 
point. Table sorted by analysis time point. Only post-baseline analysis time 
points are shown. 
 
 
LUNG FUNCTION 
 
14.3.5.1 
Spirometry: Summary of Actual Values and Changes from Baseline 
(Safety Set) 
SAF 
TPT001 
 
Descriptive statistics of spirometry parameters actual values and changes 
from baseline per parameter and analysis time point. Table sorted by 
analysis time point. Each parameter will begin on a new page. 
 
 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 54 of 65 
Number 
Title 
Analysis 
Set 
TLFs 
Library 
Template 
Number 
14.3.5.2 
Spirometry: Summary of Relative Changes from Baseline (Safety Set) 
[KFR] 
SAF 
TPT004 
 
Descriptive statistics of relative changes from baseline in spirometry 
results per parameter and analysis time point. Table sorted by analysis time 
point. Only post-baseline analysis time points are shown. 
 
 
14.3.5.3 
Diffusing Capacity: Summary of Actual Values and Changes from 
Baseline (Safety Set) 
SAF 
TPT001 
 
Descriptive statistics of diffusing capacity parameters actual values and 
changes from baseline per parameter and analysis time point. Table sorted 
by analysis time point. Each parameter will begin on a new page. 
 
 
SYSTEMIC MARKERS 
 
14.3.6.1 
Systemic Markers: Summary of Actual Values and Changes from 
Baseline (Safety Set) 
SAF 
VST001 
 
Descriptive statistics of systemic markers actual values and changes from 
baseline per parameter and analysis time-point. Table sorted by analysis 
time-point. Each parameter will begin on a new page. 
Note: if systemic reactions are detected in less than 3 subjects, this table 
will be generated without results. Instead, an informative message will be 
printed in this output. 
Template VST001 is used, using the systemic markers. 
 
 
OTHER VARIABLES 
 
TG2 IN PLASMA 
 
14.3.7.1 
TG2 in Plasma: Summary of Actual Values and Changes from 
Baseline (Safety Set) [KFR] 
SAF 
VST001 
 
Descriptive statistics of TG2 plasma levels actual values and changes from 
baseline per parameter and analysis time-point. Table sorted by analysis 
time-point. 
Template VST001 is used, using TG2 plasma levels instead. 
 
 
 
 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 55 of 65 
9.2 
LISTINGS 
Number 
Title 
Analysis 
Set 
TLFs 
Library 
Template 
Number 
GENERAL CHARACTERISTICS 
 
16.1.7 
Randomisation Schedule (Randomised Set) 
RND 
DSL001 
 
Listing of subject numbers and randomisation information  
All discrepancies (as-randomised versus as-treated) will be presented. 
 
 
16.2.1.1 
Screening Failures (Enrolled Set) 
ENR 
DSL002 
 
Listing of all subjects not randomised. The study discontinuation reason 
and demographic data will be listed. 
 
 
16.2.1.2 
Study Discontinuation After Randomisation (Randomised Set) 
RND 
DSL003 
 
Listing of all subjects that discontinued after randomisation. The study 
discontinuation reason will also be listed. 
 
 
16.2.1.3 
Subject Disposition (Randomised Set) 
RND 
DSL004 
 
Listing of the reasons for completion / discontinuation and the number of 
days since first study treatment administration at study discontinuation. 
In case the discontinuation was due to AE, the AE will be presented in 
this listing. If there is another explanation on the discontinuation reason 
collected in the eCRF, this will also be presented in this listing. 
 
 
16.2.1.4 
Randomisation Code Broken (Randomised Set) 
RND 
DSL005 
 
Listing of the code breaking information. Only subjects for which the 
code was broken are presented in this listing. 
 
 
16.2.1.5 
Subject Disposition: Analysis Phases With Time (Randomised Set) 
RND 
DSL008 
 
Listing of the phases in the study (definition with time for adverse events 
and medications), together with the start and end date(time)s. 
 
 
16.2.1.6 
Subject Disposition: Analysis Phases Without Time (Randomised 
Set) 
RND 
DSL008 
 
Listing of the phases in the study (definition without time for 
procedures), together with the start and end dates. 
 
 
16.2.1.7 
Study Visits (Randomised Set) 
RND 
SVL001 
 
Listing per subject number of all subject visits, together with the start 
and end date of each visit. Listing is sorted chronologically by visit start 
date within each subject. 
 
 
16.2.1.8 
First and Last Contact in the Study (Randomised Set) 
RND 
 
 
List of the date of the first signed ICF, last visit date and last date of 
contact in the study. All dates are presented overall, not by treatment. 
 
 
16.2.2.1 
Violation of Eligibility Criteria (Randomised Set) 
RND 
DVL001 
 
Only violated in- and exclusion criteria will be listed. Only deviations 
with DVDECOD = “VIOLATION OF INCLUSION CRITERION” or 
“VIOLATION OF EXCLUSION CRITERION” will be selected. 
 
 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 56 of 65 
Number 
Title 
Analysis 
Set 
TLFs 
Library 
Template 
Number 
16.2.2.2 
Important Protocol Deviation (Randomised Set) 
RND 
DVL002 
 
Listing of all important protocol deviations information. 
Template DLV002 is used, excluding the ‘Category’ column. 
 
 
16.2.2.3 
Restrictions (Randomised Set) 
RND 
 
 
Listing of all restrictions data available in the eCRF. 
 
 
16.2.3.1 
Analysis Set Disposition (Randomised Set) 
RND 
DSL006 
 
Listing of all subjects and analysis set indicators. 
 
 
16.2.3.2 
Subjects Excluded from Safety/PK Set (Randomised Set) 
RND 
DSL007 
 
List of all subjects that were excluded from SAF/PK/PD. 
 
 
16.2.4.1 
Demographic Characteristics (Randomised Set) 
RND 
DML001 
 
Listing of all demographic parameters 
 
 
16.2.4.2 
IPF History (Randomised Set) 
RND 
SCL001 
 
Listing of all baseline disease characteristics. 
Adjust the columns of SCL001 according to the available IPF history 
data. 
 
 
16.2.4.3 
Serology at Screening (Randomised Set) 
RND 
SCL002 
 
Listing of all results of serology tests done at screening 
 
 
16.2.4.4 
Ethanol, Urine Drug Screen and Cotinine Tests (Randomised Set) 
RND 
SCL002 
 
Listing of all results of urine drug screen tests performed 
For layout purposes, template SCL003 could be used instead. 
 
 
16.2.4.5 
Smoking Status (Randomised Set) 
RND 
SUL001 
 
Listing of all smoking data available in the eCRF 
 
 
16.2.4.6 
Medical/Surgical History (Randomised Set) 
RND 
MHL001 
 
Listing of the medical history data findings available in the eCRF 
 
 
16.2.4.7 
Concomitant Diseases (Randomised Set) 
RND 
MHL002 
 
Listing of the concomitant diseases data findings available in the eCRF 
 
 
16.2.4.8 
Procedures (Randomised Set) 
RND 
PRL001 
 
Listing of all data on prior, maintained and concomitant procedures 
 
 
16.2.4.9 
Medications (Randomised Set) 
RND 
CML001  
 
Listing of all data on prior, maintained and concomitant medications 
 
 
16.2.4.10 
Comments (Randomised Set) 
RND 
COL001 
 
Listing of all remarks and comments written in the eCRF 
 
 
16.2.5.1 
Exposure (Randomised Set) 
RND 
 
 
Listing of all data related to exposure 
 
 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 57 of 65 
Number 
Title 
Analysis 
Set 
TLFs 
Library 
Template 
Number 
PHARMACOKINETICS 
 
16.2.5.2 
Actual Sampling Times and Serum Concentrations (PK Set) 
PK 
PCL001 
 
Listing per subject, dose level, and planned time point of actual blood 
sampling times and serum concentrations (actual date of sampling and 
end of infusion, ‘theoretical sampling time after windowing’ (if different 
from scheduled one), and remarks (if applicable) will be presented too). 
Exclusions of concentrations will be marked. 
 
 
16.2.5.3 
PK Data Excluded from PK Analysis (PK Set) 
PK 
 
 
Listing per subject, dose level and PK parameter or concentration time 
point of the subjects that are excluded from PK set and/or PK data that is 
excluded from PK analysis, with the reason for exclusion. Exclusions 
that are due to an IDV are marked too. 
 
 
IMMUNOGENICITY 
 
16.2.6.1 
ADA Responses (Safety Set) 
SAF 
 
 
Listing for ADA positive subjects presenting at least the following 
information: subject identifier, actual dose administered, pre-existing 
ADA (i.e., baseline ADA status and titer), peak ADA titer and 
corresponding actual and nominal time point, nAb status at nominal time 
point of peak ADA, time to onset of ADA, ADA status and titer at final 
ADA assessment / last available time point, pre-dose TG2 level, TG2 
level at nominal time point of peak ADA, CHF10067 AUC0-inf; AUC0-t, 
clearance 
 
 
SAFETY 
 
ADVERSE EVENTS 
 
16.2.7.1 
Pre-Treatment Adverse Events (Randomised Set) 
RND 
AEL001 
 
Listing of all pre-treatment AE information collected in the eCRF and of 
the onset day and duration. All information of one AE will be presented 
on the same line. 
 
 
16.2.7.2 
Treatment Emergent Adverse Events (Randomised Set) 
RND 
AEL002 
 
Listing of all AE information collected in the eCRF and of the phase 
dates and onset day and duration. All information of one AE will be 
presented on the same line. 
 
 
16.2.7.3 
Serious Treatment Emergent Adverse Events (Randomised Set) 
RND 
AEL002 
 
Same as listing 16.2.7.2, but listing serious TEAEs only 
 
 
16.2.7.4 
Non-Serious Treatment Emergent Adverse Events (Randomised Set) 
RND 
AEL002 
 
Same as listing 16.2.7.2, but listing non-serious TEAEs only 
 
 
16.2.7.5 
Adverse Drug Reactions (Randomised Set) 
RND 
AEL002 
 
Same as listing 16.2.7.2, but listing ADRs only 
 
 
16.2.7.6 
Serious Adverse Drug Reactions (Randomised Set) 
RND 
AEL002 
 
Same as listing 16.2.7.2, but listing serious ADRs only 
 
 
16.2.7.7 
Grade 3 or 4 Treatment Emergent Adverse Events (Randomised 
Set) 
RND 
AEL002 
 
Same as listing 16.2.7.2, but listing grade 3 or 4 TEAEs only 
 
 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 58 of 65 
Number 
Title 
Analysis 
Set 
TLFs 
Library 
Template 
Number 
16.2.7.8 
Treatment Emergent Adverse Events Leading to Study Treatment 
Discontinuation (Randomised Set) 
RND 
AEL002 
 
Same as listing 16.2.7.2, but listing TEAEs leading to study treatment 
discontinuation only 
 
 
16.2.7.9 
Treatment Emergent Adverse Events Leading to Death 
(Randomised Set) 
RND 
AEL002 
 
Same as listing 16.2.7.2, but listing TEAEs leading to death only 
 
 
16.2.7.10 
Immediate Hypersensitivity Reactions (Randomised Set) 
RND 
AEL002 
 
Listing IHR along with associated signs/symptoms and suspected 
anaphylaxis and a reference to the related adverse event(s). 
 
 
16.2.7.11 
Physical Examination Abnormalities (Randomised Set) 
RND 
PEL001 
 
Listing of all data on abnormal physical examinations findings 
 
 
LABORATORY DATA 
 
16.2.8.1 
Laboratory Results: Haematology Full Listing (Randomised Set) 
RND 
LBL001 
 
Listing of all haematology results. The (non-imputed) values will be 
shown, as well as normal ranges, abnormality flags (L/H), clinical 
significance flag and fasted flag. Treatment-emergent abnormalities will 
be flagged. 
 
 
16.2.8.2 
Laboratory Results: Haematology Abnormalities (Randomised Set) 
RND 
LBL001 
 
Same as listing 16.2.8.1, but listing abnormal results only 
 
 
16.2.8.3 
Laboratory Results: Biochemistry Full Listing (Randomised Set) 
RND 
LBL001 
 
Same as listing 16.2.8.1, but listing biochemistry results instead 
 
 
16.2.8.4 
Laboratory Results: Biochemistry Abnormalities (Randomised Set) 
RND 
LBL001 
 
Same as listing 16.2.8.3, but listing abnormal results only 
 
 
16.2.8.5 
Laboratory Results: Urinalysis (Randomised Set) 
RND 
LBL001 
 
Listing of all urinalysis results. The (non-imputed) values will be shown, 
as well as normal ranges, abnormality flags (L/H/A), and clinical 
significance flag. 
 
 
16.2.8.6 
Laboratory Results: Pregnancy Test (Randomised Set) 
RND 
LBL005 
 
Listing of all serum and urine pregnancy results. 
 
 
VITAL SIGNS 
 
16.2.9.1 
Vital Signs: Full Listing (Randomised Set) 
RND 
VSL002 
 
Listing of all vital signs results, including oxygen saturation. The values 
will be shown, as well as changes from baseline and change 
abnormalities. Treatment-emergent abnormalities will be flagged. 
 
 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 59 of 65 
Number 
Title 
Analysis 
Set 
TLFs 
Library 
Template 
Number 
ECG 
 
16.2.10.1 
Local 12-Lead ECG: Full Listing (Randomised Set) 
RND 
EGL001 
 
Listing of all triplicate/single local 12-lead ECG results and the 
corresponding interpretation. The values will be shown, as well as 
changes from baseline and abnormality categories (for QTcF). 
Treatment-emergent abnormalities will be flagged. 
 
 
16.2.10.2 
Local 12-Lead ECG: Abnormalities (Randomised Set) 
RND 
EGL001 
 
Same as listing 16.2.10.1 but listing abnormal results only. 
Note: results are considered abnormal when the interpretation by the 
investigator is abnormal. 
 
 
LUNG FUNCTION 
 
16.2.11.1 
Lung Function: Full Listing (Randomised Set) 
RND 
VSL002 
 
Listing of all lung function results. The values will be shown, as well as 
changes and relative changes from baseline. 
Template VSL002 is used, presenting the lung function parameters 
instead. 
 
 
SYSTEMIC MARKERS 
 
16.2.12.1 
Systemic Markers: Full Listing (Randomised Set) 
RND 
VSL001 
 
Listing of all systemic markers. The values will be shown, as well as 
changes from baseline. 
Template VSL001 is used, presenting the systemic markers instead. 
 
 
OTHER VARIABLE 
 
TG2 IN PLASMA 
 
16.2.13.1 
TG2 in Plasma: Full Listing (Randomised Set) 
RND 
VSL001 
 
Listing of TG2 levels in plasma. The values will be shown, as well as 
changes from baseline. 
Template VSL001 is used, presenting the TG2 plasma levels instead. 
 
 
 
 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 60 of 65 
9.3 
FIGURES 
Number 
Title 
Analysis 
Set 
TLFs Library 
Template 
Number 
PHARMACOKINETICS 
14.2.2.1 
Mean CHF10067 Serum Concentration vs. Time Profiles (PK 
Set) 
PK 
TPF005 
 
Mean (±SD, for linear scale) CHF10067 serum concentration vs. 
time profiles. In linear-linear and log-linear scales, with a different 
plot symbol, colour, and line pattern for each dose level. 
 
 
14.2.2.2 
Dose Proportionality Assessment (PK Set) 
PK 
 
 
Individual and geometric mean PK parameter (log values) vs. log 
dose with regression line together with a 90% confidence band. 
 
 
16.2.5.1 
Individual CHF10067 Serum Concentration vs. Time Profiles, 
per Dose Level (PK Set) 
PK 
TPF006 
 
Individual CHF10067 serum concentration vs. time profiles, per dose 
level, all subjects on the same graph. One graph per dose level. In 
linear-linear and log-linear scales with a different plot symbol and 
line pattern for each subject, and a different colour for ADA 
positivity and negativity. 
 
 
IMMUNOGENICITY 
14.2.4.1 
Mean CHF10067 Serum Concentration vs. Time Profiles by 
subject ADA status (PK Set) 
PK 
TPF005 
 
Mean (±SD, for linear scale) CHF10067 serum concentration vs. 
time profiles. In linear-linear and log-linear scales, with a different 
plot symbol for each dose level and ADA subject status. 
Note: if the number of ADA+ subjects is less than 3, this figure will 
be generated without results. Instead, an informative message will be 
printed in this output. 
 
 
VITAL SIGNS 
14.3.3.1 
Mean Change from Baseline in Vital Signs and Oxygen 
Saturation (Safety Set) 
SAF 
TPF001 
 
Graph of mean changes and their 95% confidence interval, with 
“time” on the horizontal axis and a different plot symbol for each 
treatment. Each parameter will be presented separately. 
 
 
16.2.9.1 
Individual Change from Baseline in Vital Signs and Oxygen 
Saturation (Safety Set) 
SAF 
TPF002 
 
Graph of individual changes from baseline, with “time” on the 
horizontal axis and a different colour or plot symbol for each subject. 
Each treatment and parameter will be presented separately. 
 
 
ECG 
14.3.4.1 
Mean Change from Baseline in Heart Rate and QTcF (Safety 
Set) 
SAF 
TPF001 
 
Graph of mean changes, with “time” on the horizontal axis and a 
different plot symbol for each treatment. Each parameter will be 
presented separately. 
 
 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 61 of 65 
Number 
Title 
Analysis 
Set 
TLFs Library 
Template 
Number 
16.2.10.1 
Individual Change from Baseline in 12-Lead ECG (Safety Set) 
SAF 
TPF002 
 
Graph of individual changes from baseline, with “time” on the 
horizontal axis and a different colour or plot symbol for each subject. 
Each treatment and parameter will be presented separately. 
 
 
LUNG FUNCTION 
14.3.5.1 
Mean Absolute Change from Baseline in Spirometry (Safety Set) 
SAF 
TPF001 
 
Graph of mean absolute changes, with “time” on the horizontal axis 
and a different plot symbol for each treatment. 
 
 
14.3.5.2 
Mean Relative Change from Baseline in Spirometry (Safety Set) 
SAF 
TPF001 
 
Graph of mean relative changes, with “time” on the horizontal axis 
and a different plot symbol for each treatment. 
 
 
14.3.5.3 
Mean Absolute Change from Baseline in Diffusing Capacity 
(Safety Set) 
SAF 
TPF001 
 
Graph of mean absolute and relative changes, with “time” on the 
horizontal axis and a different plot symbol for each treatment. 
 
 
OTHER VARIABLE 
TG2 IN PLASMA 
14.3.6.1 
Mean Actual Values of TG2 in Plasma (Safety Set) 
SAF 
TPF001 
 
Graph of mean actual values, with “time” on the horizontal axis and 
a different plot symbol for each treatment. 
 
 
16.2.11.1 
Individual Actual Values of TG2 in Plasma (Safety Set) 
SAF 
TPF002 
 
Graph of individual actual values, with “time” on the horizontal axis 
and a different colour or plot symbol for each subject. ADA 
positivity/negativity will be shown using different colours. Each 
treatment will be presented in a different plot. 
 
 


Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 62 of 65 
10. 
APPENDICES 
10.1 
SAS CODE 
The SAS code in this section is an example and might differ from the actual code 
used in the statistical analysis. 
Dose proportionality on CHF10067 serum PK parameters:  
proc mixed data=dataset; 
 
by param  
model logPK = logDOSE;  
estimate 'slope' logDOSE 1 / cl alpha = 0.1;  
ods output estimates = diff; 
run; 
 
Notes: 
• Dataset: analysis dataset of PK parameters. One record per subject per 
parameter; 
• Param (character): PK parameter name and/or identifier; 
• LogPK (numeric): log value of PK parameter; 
• LogDOSE (numeric): log value of doses (1000mg; 2000mg; 3000mg). 
 






Statistical Analysis Plan 
 
CLI-10067AA1-01 
Final Analysis 
Final 1.0  of 30MAY2024 
 
Page 65 of 65 
 
10.3 
DICTIONARY VERSIONS 
 
Data 
Dictionary 
Adverse Events 
MedDRA version 25.0 
Concomitant Therapy 
WHO-DD version 01 Mar 2022 (Global) 
Format B3 
Anatomical-Therapeutic-Chemical 
(ATC) selection 
WHO-DD version 01 Mar 2022 (Global) 
Format B3 
Medical History 
MedDRA version 25.0 
Procedures 
MedDRA version 25.0 
Clinical Events 
MedDRA version 25.0