Single Arm, Open-Label, Multicenter, Registry Study of Revcovi (Elapegademase-lvlr) Treatment in ADA-SCID Patients Requiring Enzyme Replacement Therapy
Conditions: Adenosine Deaminase Severe Combined Immunodeficiency
Sponsor: Chiesi Farmaceutici S.p.A.

SIGNATURE PAGE
 
Document Code: CLI-06814AA1-01-APP 16.1.1-02403
Title: Revcovi registri_Protocol_Single Arm, Open-Label, Multicenter, Registry Study of Revcovi
(elapegademase-lvlr) Treatment in ADA-SCID Subjects Requiring Enzyme Replacement Therapy
Version: 5.0,CURRENT
Status:Approved, since: 22-Feb-2022 14:32:08   UTC
 
 
 
Electronic Signature:
Signed by: Tricta Fernando (F.TRICTA)
Date: 22-Feb-2022 14:09:52   UTC
Meaning of Signature: Clinical Approval
 
Signed by: Zhao Feng (F.ZHAO)
Date: 22-Feb-2022 14:28:12   UTC
Meaning of Signature: Statistician Approval
 
Signed by: Fradette Caroline (C.FRADETTE)
Date: 22-Feb-2022 14:31:58   UTC
Meaning of Signature: Clinical Approval
 
 
Note:  Each electronic signature above is equivalent to a handwritten signature since the
computer system managing the electronic document fully complies with the international rules
(i.e. FDACFR21part11, EU Annex11) concerning Electronic Records and Electronic Signatures
Management.
 
Confidential Declaration
This document contains confidential data which is the property of Chiesi. The use of this data or any
part of it must be authorized by the Department Head/Study Responsible. A secrecy agreement must
be set up and signed prior to disclosing any content of the document to a Third Party.

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 1 of 85
Date: 04th February 2022
Clinical Research Protocol
Sponsor:  
Chiesi Farmaceutici S.p.A.
Via Palermo 26/A
43122, Parma
Italy
Protocol  CLI-06814AA1-01
Phase IV
Single Arm, Open-Label, Multicenter, Registry Study of Revcovi (elapegademase-lvlr) 
Treatment in ADA-SCID Subjects Requiring Enzyme Replacement Therapy
Version 5.0
The information contained in this document, particularly unpublished data, is the 
property or under control of Chiesi Farmaceutici S.p.A.., and is provided to you in 
confidence as an investigator, potential investigator, or consultant, for review by you, 
your staff, and an applicable Institutional Review Board or Independent Ethics 
Committee.  The information is only to be used by you in connection with authorized 
clinical studies of the study product described in the protocol.  You will not disclose 
any of the information to others without written authorization from Chiesi 
Farmaceutici S.p.A., except to the extent necessary to obtain informed consent from 
those persons to be enrolled in this study..

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 2 of 85
Date: 04th February 2022
1
TABLE OF CONTENTS
1
TABLE OF CONTENTS...................................................................................2
2
STUDY SYNOPSIS..........................................................................................8
3
LIST OF ABBREVIATIONS............................................................................15
4
GENERAL STUDY INFORMATION...............................................................17
5
INTRODUCTION............................................................................................19
5.1
Disease Background .....................................................................................19
5.2
Description of the Study Product...................................................................21
5.3
Product Background Information...................................................................22
5.3.1
Non-Clinical Experience..............................................................................22
5.3.2
Clinical Experience .....................................................................................25
5.4
Target Population and Study Rationale.........................................................27
5.5
Potential Risks and Benefits..........................................................................27
6
STUDY PURPOSE, OBJECTIVES AND ENDPOINTS .................................28
6.1
Purpose .........................................................................................................28
6.2
Objectives......................................................................................................28
6.3
Endpoints ......................................................................................................28
7
STUDY DESIGN ............................................................................................29
7.1
Overview of Study Design.............................................................................29
7.2
Study Treatments..........................................................................................30
7.3
Assignment of Subjects to Treatment ...........................................................30
7.4
Study Duration...............................................................................................30
7.5
Methods to Minimize Bias .............................................................................31
7.6
Appropriateness of Study Measurements .....................................................31
7.7
Study Monitoring Committees .......................................................................31
8
Revcovi ..........................................................................................................31
8.1
Description of Revcovi...................................................................................31
8.2
Supply and Labeling......................................................................................32
8.3
Storage Conditions (See Revcovi PI)............................................................32
8.4
Preparation for Administration (See Revcovi PI)...........................................32
8.5
Procedure for Unblinding...............................................................................32
8.6
Revcovi Accountability ..................................................................................32
9
STUDY POPULATION...................................................................................32

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 3 of 85
Date: 04th February 2022
9.1
Number of Subjects.......................................................................................32
9.2
Inclusion Criteria............................................................................................32
9.3
Exclusion Criteria ..........................................................................................33
9.4
Post-enrollment Restrictions .........................................................................33
9.4.1
Concomitant Medications............................................................................33
9.4.2
Dietary Restrictions.....................................................................................33
9.5
Withdrawal of Enrolled Subjects....................................................................33
9.5.1
Withdrawal Criteria......................................................................................33
9.5.2
Withdrawal Procedures...............................................................................34
9.5.3
Replacement of Discontinued Subjects ......................................................34
10
DESCRIPTION OF STUDY PROCEDURES AND VARIABLES ...................34
10.1
Informed Consent..........................................................................................34
10.2
Screening and Enrollment.............................................................................35
10.3
History and Baseline Characteristics.............................................................35
10.4
Maximum Total Blood Collection Volume......................................................36
10.5
Safety Procedures.........................................................................................36
10.5.1
Physical Examination ..............................................................................36
10.5.2
Vital Signs................................................................................................36
10.5.3
Safety Laboratory Assessments..............................................................36
10.5.4
Immunogenicity .......................................................................................37
10.5.5
Adverse Event Assessment.....................................................................37
10.6
Biochemical Variables for Dose Adjustments and Efficacy...........................38
10.6.1
Trough Plasma ADA Activity ...................................................................38
10.6.2
Erythrocyte dAXP ....................................................................................38
10.7
Immune Status ..............................................................................................38
10.7.1
Lymphocyte Subset Analysis...................................................................38
10.7.2
Immune Function analysis.......................................................................38
10.8
Clinical Status................................................................................................38
10.8.1
Infections .................................................................................................38
10.8.2
Hospitalizations .......................................................................................39
10.8.3
Growth.....................................................................................................39
10.8.4
Overall Survival .......................................................................................39
10.9
Quality of Life ................................................................................................39

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 4 of 85
Date: 04th February 2022
10.10
Revcovi Administration and Compliance.......................................................39
10.10.1
Dosage and Administration .....................................................................39
10.10.2
Dose Adjustments ...................................................................................40
10.10.3
Treatment Delays ....................................................................................40
10.10.4
Assessment of Revcovi Compliance .......................................................41
10.11
Assessment of Concomitant Medications of Interest ....................................41
10.12
Protocol Adherence.......................................................................................41
11
SCHEDULE OF STUDY PROCEDURES......................................................41
11.1
Enrollment .....................................................................................................41
11.2
Revcovi Treatment Period.............................................................................42
11.2.1
Adagen-transitioning subjects .................................................................42
11.2.2
Adagen-naïve subjects............................................................................50
11.3
Study Completion..........................................................................................62
12
ADVERSE EVENTS.......................................................................................62
12.1
Assessment Period .......................................................................................62
12.2
Definitions......................................................................................................62
12.2.1
Adverse Event .........................................................................................62
12.2.2
Unexpected Adverse Event.....................................................................63
12.2.3
Serious Adverse Event............................................................................63
12.2.4
Relationship to Revcovi...........................................................................63
12.2.5
Severity (Intensity)...................................................................................64
12.3
Reporting of Adverse Events.........................................................................64
12.4
Reporting of Serious Adverse Events ...........................................................65
12.5
Reporting of Pregnancy.................................................................................65
13
STATISTICS ..................................................................................................66
13.1
Sample Size Determination...........................................................................66
13.2
Statistical Methodology .................................................................................66
13.2.1
Level of Significance................................................................................66
13.2.2
Analysis Populations ...............................................................................66
13.2.3
Data Analysis...........................................................................................66
13.2.4
Handling Missing, Repeated, Unused and Spurious Data ......................69
13.2.5
Reporting of Deviations to Statistical Methodology .................................69
13.3
Interim Analyses............................................................................................69

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 5 of 85
Date: 04th February 2022
13.4
Statistical Criteria for Termination of the Study.............................................69
14
ADMINISTRATIVE.........................................................................................70
14.1
Changes to Study Protocol............................................................................70
14.1.1
Protocol Amendments .............................................................................70
14.1.2
Protocol Deviations..................................................................................70
14.2
Study Termination .........................................................................................70
14.3
Ethics Compliance Statement .......................................................................71
14.3.1
Institutional Review Board/Ethics Committee..........................................71
14.3.2
Informed Consent....................................................................................71
14.3.3
Health Insurance Portability and Accountability Act for studies conducted 
in the US 72
14.3.4
Confidentiality of Subject Records...........................................................72
14.4
Conflict of Interest .........................................................................................73
14.4.1
Monitoring and Audits..............................................................................73
14.5
Investigator Obligations.................................................................................73
14.6
Financial Disclosure ......................................................................................74
14.7
Quality Control and Quality Assurance of Study Data...................................75
14.7.1
Data Processing and Data Quality Assurance ........................................75
14.8
Study Records...............................................................................................75
14.8.1
Regulatory Documentation......................................................................75
14.8.2
Source Documents..................................................................................76
14.8.3
Case Report Forms .................................................................................76
14.8.4
Access to Study Records ........................................................................77
14.8.5
Records Retention...................................................................................77
14.9
Publication Policy ..........................................................................................77
14.10
Financing and Insurance...............................................................................77
15
INVESTIGATOR AGREEMENT.....................................................................78
16
REFERENCES...............................................................................................79
Appendix 1:
Suggested Schedule of Assessments for Adagen-Transitioning 
Subjects.........................................................................................................80
Appendix 1: Suggested Schedule of Assessments for Adagen-Transitioning Subjects 
(cont.)..........................................................................................................................82
Appendix 2:
Suggested Schedule of Assessment for Adagen-Naïve Subjects .......83

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 6 of 85
Date: 04th February 2022
Appendix 2:
Suggested Schedule of Assessment for Adagen-Naïve Subjects 
(continued) ....................................................................................................84

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 7 of 85
Date: 04th February 2022
List of Figures
Figure 1
Biochemical Defects in ADA Deficiency ..................................................................20

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 8 of 85
Date: 04th February 2022
2
STUDY SYNOPSIS
Study Drug:  Revcovi 
(elapegademase-lvlr)
IND No.:  100,687
Protocol No.: 
 CLI-06814AA1-
01
Development 
Phase:  IV
Indication: 
ADA-deficient severe 
combined 
immunodeficiency
Protocol Title: Single Arm, Open-Label, Multicenter, Registry 
Study of Revcovi (elapegademase-lvlr) Treatment in ADA--SCID 
Subjects Requiring Enzyme Replacement Therapy
Country: 
USA
No. of centers: 
13
Expected Study 
Duration: A minimum of 
24 months per subject
Study Objectives: 
To conduct a registry study on patients with adenosine deaminase 
severe combined immune deficiency (ADA-SCID) treated with 
Revcovi™ and have periodic clinical and biochemical assessments 
for safety and dose adjustment based on adenosine deaminase 
(ADA) activity and erythrocyte deoxyadenosine nucleotide (dAXP) 
levels.
Study Design and Methodology: 
Protocol CLI-06814AA1-01 is designed as a single arm, open-label, 
multicenter registry study.  The study will include ADA-SCID 
patients requiring Revcovi as Enzyme Replacement Therapy (ERT). 
This is inclusive of:

patients currently receiving chronic ERT with Adagen®; and 
transitioned/transitioning to Revcovi

infants diagnosed via newborn screening and/or definitive 
testing for ADA deficiency prescribed Revcovi

patients receiving Revcovi while preparing for 
Hematopoietic Stem Cell Transplant (HSCT) or 
Hematopoietic Stem Cell Gene Therapy (HSC-GT)

subjects who decline, are ineligible or do not respond to 
HSCT or HSC-GT and resume/start Revcovi.
Subjects for whom written informed consent/assent is obtained will 
be assigned an identification number and undergo enrollment 
procedures.  The date of ICF signature is considered the date of 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 9 of 85
Date: 04th February 2022
Study Drug:  Revcovi 
(elapegademase-lvlr)
IND No.:  100,687
Protocol No.: 
 CLI-06814AA1-
01
Development 
Phase:  IV
Indication: 
ADA-deficient severe 
combined 
immunodeficiency
Protocol Title: Single Arm, Open-Label, Multicenter, Registry 
Study of Revcovi (elapegademase-lvlr) Treatment in ADA--SCID 
Subjects Requiring Enzyme Replacement Therapy
enrollment into the registry. Subjects should have initial, trough 
erythrocyte dAXP levels and plasma ADA activity measurements 
collected prior to start of Revcovi as part of standard of care. 
Additionally, at enrollment, physical examination, vital signs, and 
laboratory values for total lymphocytes and subset analysis, as well 
as quantitative immunoglobulins, should be collected as per 
standard of care.  Subjects who started treatment with Revcovi 
before enrollment should have data collected retrospectively in 
accordance with the Suggested Schedule of Assessments.
Subjects/Parents/Caregivers/Health Care Providers will administer 
weekly intramuscular (IM) dose(s) of Revcovi and will be followed 
according to the Suggested Schedule of Assessments for trough 
dAXP and ADA activity as deemed appropriate by the provider. 
Treatment dosing and monitoring will be individualized per 
provider and subject characteristics in adherence with each study 
sites’ standards of care.
The Phase III Study STP-2279-002 was an open-label, multicenter, 
single-arm, one-way crossover study to determine the safety, 
efficacy, and PK of Revcovi (EZN2279; Succinimidyl Carbamate-
Polyethylene Glycol Recombinant Adenosine Deaminase [SC-PEG 
rADA]; elapegademase) in patients with ADA-SCID who were 
currently being treated with Adagen. All participants from the Phase 
III Study, who are now under treatment with commercial Revcovi, 
are permitted to enroll and proceed directly to the Treatment Month 
6 Visit of this study protocol (CLI-06814AA1-01). 
Enrolled subjects will be followed until the last enrolled patient has 
reached a minimum of 24 months of Revcovi treatment or until 
undergoing HSCT or HSCGT, whichever occurs first.  Subjects 
undergoing HSCT or HSCGT will be followed one month and again 
at 6 months after last Revcovi dose to assess adverse events (AEs) 
and survival. 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 10 of 85
Date: 04th February 2022
Study Drug:  Revcovi 
(elapegademase-lvlr)
IND No.:  100,687
Protocol No.: 
 CLI-06814AA1-
01
Development 
Phase:  IV
Indication: 
ADA-deficient severe 
combined 
immunodeficiency
Protocol Title: Single Arm, Open-Label, Multicenter, Registry 
Study of Revcovi (elapegademase-lvlr) Treatment in ADA--SCID 
Subjects Requiring Enzyme Replacement Therapy
Throughout the duration of the study, subjects will be assessed 
continually for AEs. 
An interim analysis will be performed approximately two years 
after study initiation.
Sample Size:
No formal sample size is calculated for this study. The study will 
enroll all eligible patients over a minimum of 2 years.
Patient Selection Criteria:
Inclusion Criteria

Patients currently receiving chronic ERT with Adagen®; 
and transitioned/transitioning to Revcovi;

Infants diagnosed via newborn screening and/or 
definitive testing for ADA deficiency prescribed 
Revcovi;

Patients receiving Revcovi while preparing for 
Hematopoietic Stem Cell Transplant (HSCT) or 
Hematopoietic Stem Cell Gene Therapy (HSC-GT);

Patients who decline, are ineligible or do not respond to 
HSCT or HSC-GT and resume/start Revcovi.
 Exclusion Criteria

Any condition that, in the opinion of the Investigator, 
makes the subject unsuitable for the study.
Study Duration:
Enrolled subjects will be followed until the last enrolled patient has 
reached 24 months of Revcovi treatment  or until undergoing HSCT 
or HSCGT, whichever occurs first. Subjects undergoing HSCT or 
HSCGT will be followed one month and again at six months after 
final Revcovi dose to assess for AEs and survival.

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 11 of 85
Date: 04th February 2022
Study Drug:  Revcovi 
(elapegademase-lvlr)
IND No.:  100,687
Protocol No.: 
 CLI-06814AA1-
01
Development 
Phase:  IV
Indication: 
ADA-deficient severe 
combined 
immunodeficiency
Protocol Title: Single Arm, Open-Label, Multicenter, Registry 
Study of Revcovi (elapegademase-lvlr) Treatment in ADA--SCID 
Subjects Requiring Enzyme Replacement Therapy
Revcovi - Dose, Route of Administration, and Duration of 
Administration:
Subjects previously treated with Adagen and Adagen-naïve subjects 
(newborn) should be dosed in accordance with the Revcovi Package 
Insert (PI) recommendation.  Subjects who started Revcovi 
treatment prior to study enrollment should continue to be dosed in 
accordance with provider or Revcovi PI recommendation.
Subjects transitioning from Adagen to Revcovi:  
For subjects currently receiving Adagen at ≤ 30 U/kg/wk or an 
unknown Adagen dose, the recommended weekly IM dose of 
Revcovi is 0.2 mg/kg. 
For subjects currently receiving Adagen at > 30 U/kg/wk an 
equivalent Revcovi dose (mg/kg) can be calculated using the 
following equation:
The total weekly dose may be divided and administered in multiple 
IM injections per week.  The weekly Revcovi dose may be 
increased by increments of 0.033 mg/kg, if trough ADA activity is 
under 30 mmol/hr/L, dAXP is above 0.02 mmol/L, and/or the 
immune reconstitution is inadequate based on the clinical 
assessment of the subject by the investigator. 
Adagen-naïve subjects: The starting weekly IM dose with Revcovi 
is 0.4 mg/kg based on ideal body weight, divided into two doses 
(0.2 mg/kg twice a week), for a minimum of 12 to 24 weeks until 
immune reconstitution is achieved.  After that, the dose may be 
gradually adjusted to maintain trough ADA activity over 
30 mmol/hr/L, dAXP under 0.02 mmol/L, and/or to maintain 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 12 of 85
Date: 04th February 2022
Study Drug:  Revcovi 
(elapegademase-lvlr)
IND No.:  100,687
Protocol No.: 
 CLI-06814AA1-
01
Development 
Phase:  IV
Indication: 
ADA-deficient severe 
combined 
immunodeficiency
Protocol Title: Single Arm, Open-Label, Multicenter, Registry 
Study of Revcovi (elapegademase-lvlr) Treatment in ADA--SCID 
Subjects Requiring Enzyme Replacement Therapy
adequate immune reconstitution based on clinical assessment of the 
subject.
The optimal long-term dose and schedule of administration should 
be established by the treating physician for each subject 
individually and may be adjusted based on the laboratory values for 
trough plasma ADA activity, trough erythrocyte dAXP level, and/or 
on the treating physician’s medical assessment of the subject’s 
clinical status.
Reference Therapy, Dose Route of Administration and 
Duration of Administration: Not applicable
Criteria for Evaluation:
Biochemical Variables and Immune Status: Total erythrocyte dAXP 
from a trough blood sample; trough plasma ADA activity; immune 
status (B-, T-, and natural killer (NK) lymphocyte subset analysis; 
quantitative immunoglobulin concentration [IgA, IgG, IgM]); and 
immune function measurement, as indicated (phytohaemagglutinin 
[PHA] stimulation or equivalent). 
Safety Variables: AEs, serious adverse events (SAEs), vital signs 
and safety laboratory evaluations will be assessed in accordance 
with the Investigator’s standard of care. Immunogenicity of Revcovi 
should be assessed based on the Revcovi PI recommendations. 
Clinical Status: Clinical signs and symptoms from physical 
examination (including height and weight for growth assessment), 
incidence and duration of hospitalizations, infections (clinically and 
microbiologically documented, including opportunistic infections), 
and survival (follow up visits and/or phone calls to confirm subject 
status).
Quality of Life: Quality of life (QOL) will be assessed for subjects 
up to and including those who are 18 years old using the age-
specific Pediatric Quality of Life Inventory (PedsQL).  Subjects 
over 18 years old will be assessed using the SF-36 and Primary 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 13 of 85
Date: 04th February 2022
Study Drug:  Revcovi 
(elapegademase-lvlr)
IND No.:  100,687
Protocol No.: 
 CLI-06814AA1-
01
Development 
Phase:  IV
Indication: 
ADA-deficient severe 
combined 
immunodeficiency
Protocol Title: Single Arm, Open-Label, Multicenter, Registry 
Study of Revcovi (elapegademase-lvlr) Treatment in ADA--SCID 
Subjects Requiring Enzyme Replacement Therapy
Antibody Deficiency Quality of Life Questionnaire (PADQOL). 
QOL assessment data will be collected from study participants via 
scripted phone calls by the study call center and the QOL responses 
will be entered directly into the electronic data capture (EDC) 
system. QOL assessments will be collected prospectively for 24 
months after starting Revcovi. 
Statistical Methodology: 
As this is a registry study, analyses will be descriptive, with data 
listings, graphical presentations, frequency tabulations, and 
summary statistics as appropriate. 
Biochemical Analysis:
Following recommendations from the Revcovi PI, Erythrocyte 
dAXP concentration should be maintained at ≤ 0.02 μmol/mL and 
trough plasma ADA activity at ≥ 30 μmol/h/mL for Adagen-treated 
subjects transitioning to Revcovi and for Adagen-naïve subjects.
Analyses of the following biochemical parameters will be 
primarily descriptive, with data listings, graphical presentations, 
frequency tabulations, and summary statistics as appropriate: total 
erythrocyte dAXP, trough plasma ADA activity, absolute 
lymphocyte count, B-, T-, and NK-lymphocyte subset analysis; 
quantitative immunoglobulin concentration, and immune 
reconstitution data. Change from baseline will be calculated and 
summary statistics provided for all applicable parameters.
Safety Analysis:

AEs will be coded according to most recent version of Medical 
Dictionary for Regulatory Activities (MedDRA) and will be 
summarized in frequency tables displaying counts and 
percentage by body system, preferred term, and treatment groups 
as naïve patients or patients transitioning from Adagen.  In 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 14 of 85
Date: 04th February 2022
Study Drug:  Revcovi 
(elapegademase-lvlr)
IND No.:  100,687
Protocol No.: 
 CLI-06814AA1-
01
Development 
Phase:  IV
Indication: 
ADA-deficient severe 
combined 
immunodeficiency
Protocol Title: Single Arm, Open-Label, Multicenter, Registry 
Study of Revcovi (elapegademase-lvlr) Treatment in ADA--SCID 
Subjects Requiring Enzyme Replacement Therapy
addition, AEs will be summarized by relationship to Revcovi 
and by severity.  All SAEs will also be summarized in a 
frequency table. 

Safety laboratory parameters (chemistry, hematology, and 
urinalysis) will be summarized descriptively at each time point; 
out-of-range values will be listed.

Vital sign parameters will be summarized descriptively at each 
time point.
Clinical Status: These endpoints will be summarized descriptively:

Incidence of infection

Incidence and duration of hospitalizations

Growth: Height-for-age and weight-for-age Z-scores

Survival: Descriptive summary of subject status.
Quality of Life Analysis:
Quality of Life: QOL will be assessed for subjects up to and 
including those who are 18 years old using the age-specific 
Pediatric Quality of Life Inventory (PedsQL).  Subjects over 
18 years old will be assessed using the SF-36 and Primary 
Antibody Deficiency Quality of Life Questionnaire (PADQOL). 
Data will be summarized by age and stratified by previous 
participation in the Phase III study STP-2279-002.  Subjects that 
age out of PedsQL and into PADQOL will be summarized only in 
the PedsQL while their PADQOL will be listed. 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 15 of 85
Date: 04th February 2022
3
LIST OF ABBREVIATIONS
Abbreviation
Term
ADA
adenosine deaminase
ADA-SCID
adenosine deaminase severe combined immunodeficiency
AE
adverse event
aPTT
activated partial thromboplastin time
AUC
area under the curve
Cmax
maximum concentration
CMV
cytomegalovirus
CRF
case report form
Cys74
cysteine at position 74 
C74S
Cys74 mutated to serine 
d-adenosine
2´-deoxyadenosine
d-ATP
2´-deoxyadenosine 5´-triphosphate
dAXP
deoxyadenosine nucleotides
DCF
data clarification forms
dCydK
deoxycytidine kinase
d-inosine
2´-deoxyinosine
DNA
deoxyribonucleic acid
DSMC
Data and Safety Monitoring Committee
EDTA
ethylenediaminetetraacetic acid 
ERT
Enzyme Replacement Therapy
FACS
fluorescence-activated cell sorter
FDA
Food and Drug Administration
GCP
Good Clinical Practice
GLP
Good Laboratory Practice
HIPAA
Health Insurance Portability and Accountability Act
HLA
human leukocyte antigen 
HSC-GT
hematopoietic stem cell gene therapy

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 16 of 85
Date: 04th February 2022
HSCT
hematopoietic stem cell transplantation
IEC
Independent Ethics Committee
Ig
immunoglobulin
IM
intramuscular
IND
Investigational New Drug 
IP
intraperitoneal
IRB
Institutional Review Board
MedDRA
Medical Dictionary for Regulatory Activities
mPEG
monomethoxypolyethylene glycol
Mg
milligram
MPV
mean platelet volume 
NK
natural killer
NOAEL
no observed adverse effect levels
PADQOL
Primary Antibody Deficiency Quality of Life Questionnaire
PD
pharmacodynamic
PedsQL
Pediatric Quality of Life Inventory
PEG
polyethylene glycol
PHI
protected health information
PI
package insert
PK
pharmacokinetic
QC
quality control
rADA
recombinant adenosine deaminase
SAE
serious adverse event
SC
succinimidyl carbamate
SF-36
Short Form 36 Health Survey
SS
succinimidyl succinate
SST
serum separator tube 
t1/2
Terminal elimination half life
TSE
transmissible spongiform encephalopathy

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 17 of 85
Date: 04th February 2022
4
GENERAL STUDY INFORMATION
Sponsor Name:
Chiesi Farmaceutici S.p.A.
Sponsor Address: 
Via Palermo 26/A
43122, Parma Italy
Phone: 
+39 0521 2791
Fax: +39 0521 774468
E-mail: info@chiesigroup.com
*also reported as Chiesi throughout 
Sponsor Medical Expert: 
Fernando Tricta, MD
Chiesi Canada Corporation
44 Chipman Hill
Suite 1000 Saint John
New Brunswick E2L 2A9
Phone: 1 (800) 854-3534
E-mail: f.tricta@chiesi.com
Readily available in case of medical questions
Clinical Program Leader:
Caroline Fradette
Chiesi Canada Corporation
44 Chipman Hill
Suite 1000 Saint John
New Brunswick E2L 2A9
Phone: 1 (800) 854-3534
Mobile : 1 (514) 451-1217
E-mail: c.fradette@chiesi.com
Clinical Project Manager:  
Chiara Franke
Chiesi Farmaceutici S.p.A.
Via Palermo 26/A
43122 Parma Italy

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 18 of 85
Date: 04th February 2022
Phone: +39  039 2280660 
E-mail: c.franke.consultant@chiesi.com    
 
CRO (For Data Management and Statistics activities): United Biosource Corporation (UBC)
920 Harvest Drive
Blue Bell, PA 19422

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 19 of 85
Date: 04th February 2022
5
INTRODUCTION
Leadiant Biosciences, Inc. (Leadiant Biosciences) developed and received Food and Drug 
Administration (FDA) approval (BLA 761092) for Revcovi™ (elapegademase-lvlr), a 
polyethylene glycol recombinant adenosine deaminase [PEG-rADA], for the treatment of 
pediatric and adult subjects with adenosine deaminase severe combined immunodeficiency 
(ADA-SCID) on October 2017. In November 2020 Chiesi Farmaceutici S.p.A (Chiesi) bought 
the rights of Revcovi™ from Leadiant Biosciences. The change in IND ownership has been 
communicated to FDA with notification submitted to the IND by Chiesi on 23 Nov 2020.
5.1
Disease Background
Adenosine deaminase (ADA)-deficient combined immunodeficiency disease is a rare, 
inherited, and often fatal disease.  It is characterized by severe and recurrent opportunistic 
infections, failure to thrive, profound lymphopenia with absent or severely impaired cellular 
and humoral immune function, and metabolic abnormalities (Booth and Gaspar 2009, Gaspar 
et al., 2009).  These patients are lymphopenic at birth and predisposed to recurrent illnesses 
caused by pathogens and opportunistic organisms that often begin within a few weeks.  The 
average age at diagnosis for patients with ADA-SCID is within first few months of life 
(Arredondo-Vega et al., 1998).  The incidence of ADA deficiency is estimated to be between 
1:200,000 and 1:1,000,000 live births (Gaspar et al., 2009).  
ADA deficiency can be categorized into four phenotypes (Booth and Gaspar 2009): 

Early onset: The largest number of patients with ADA deficiency (about 85% to 90%) 
present with early onset ADA-SCID, which is the most severe form of the 
immunodeficiency. Patients are usually diagnosed within first few months of life and 
almost always by the age of 1 year.  

Delayed onset ADA deficiency has been identified in 10% to 15% of patients with ADA 
deficiency.  The disease presents itself after the first year of life and is most likely related 
to the specific ADA mutation that in such cases results in some residual ADA activity and 
less profound lymphopenia and immune function. 

Late (or adult) onset ADA deficiency has been identified in some individuals but is less 
common than early or delayed-onset forms. 

Partial ADA deficiency can be an incidental finding in a healthy individual who has 
normal immune function and abnormal ADA expression in erythrocytes. Partial ADA 
deficiency is extremely rare.
Patients with ADA-SCID are unable to produce sufficient ADA enzyme in their cells because 
of mutations in the ADA gene on chromosome 20q.  ADA deficiency is a disorder of purine 
salvage (Booth et al., 2007).  In the absence of this enzyme, the purine substrates adenosine, 
2´-deoxyadenosine, and their metabolites reach unusually high levels in cells and are toxic to 
lymphocytes (see Figure 1) (Qasim et al., 2004).  Thus, deficiency of the ADA enzyme is the 
underlying defect that leads to the buildup of toxic metabolites, which in turn affect different 
organ systems, most notably the immune system (Gaspar et al., 2009).  It is still not entirely 
clear whether ADA-deficient patients have intrinsically abnormal lymphocytes or whether the 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 20 of 85
Date: 04th February 2022
defects seen are secondary to the effect of accumulation of 2´-deoxydenosine and adenosine 
(Gaspar et al., 2009).  In addition, accumulation of toxic metabolites also may interfere with 
thymic stroma development, maturation, and function, resulting in impaired ability to support 
T-cell development (Gaspar et al., 2009). Finally, the decrease in S-Adenosyl homocysteine 
hydrolase also has some impact as a result of the ADA deficiency on critical transmethylation 
cellular reactions contributing to lymphocyte dysfunction.
Absence of the enzyme ADA allows accumulation of toxic metabolites, resulting in complete 
or partial deficiency of both cell-mediated and humoral immunity (Booth and Gaspar 2009).
Figure 1 Biochemical Defects in ADA Deficiency
ADA is expressed in all tissues of the body. In normal cells, DNA turnover is mediated by ADA catalyzing the 
deamination of d-adenosine to d-inosine. In ADA-deficient cells, there is an accumulation of d-adenosine, which 
is then converted by dCydK to d-ATP. The build-up of these two metabolites has profound effects on lymphocyte 
development and function – through effects on DNA synthesis, impaired cell division, and apoptosis – causing 
immunological defects. 
Source: (Qasim et al., 2004)
ADA = adenosine deaminase; d-adenosine = 2´-deoxyadenosine; d-ATP = 2´-deoxyadenosine 5´-triphosphate; 
dCydK = deoxycytidine kinase; d-inosine = 2´-deoxyinosine; DNA = deoxyribonucleic acid.
Patients with ADA deficiency are unable to produce the ADA enzyme in their cells.  Without 
treatment, ADA-SCID is usually fatal in the first year of life, and therefore early intervention 
is required (Gaspar et al., 2009).  ADA enzyme therapy is key to the successful detoxification 
of metabolic substrates and promotion of immune recovery in these patients (Gaspar et al., 
2009).  The ADA enzyme can be delivered in the form of allogeneic wild-type cells (donor 
stem cell transplantation), gene-modified autologous cells, or exogenous direct enzyme 
replacement therapy (ERT) (Gaspar et al., 2009).
Hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen (HLA)-
identical sibling donor is the treatment of choice for ADA-SCID as it is well tolerated and 
results in long-term correction of the immunodeficiency in ADA deficiency.  However, HSCT 
does not prevent non-immune complications of the disease (Gaspar et al., 2009).  In the absence 
of a suitable matched donor, parental haploidentical transplants are associated with greater 
complications and sometimes, poorer long-term immune recovery (Gaspar and Thrasher 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 21 of 85
Date: 04th February 2022
2005).  Completing a successful bone marrow transplant depends upon finding a matched 
donor, but the probability of this is relatively low.  ADA enzyme therapy is thus considered 
for patients lacking HLA-matched bone marrow donors and for patients whose clinical status 
places them at high risk for transplant-associated morbidity (Taupin 2006). 
Hematopoietic stem cell gene therapy (HSC-GT) using gamma retroviral vectors for the 
treatment of ADA-SCID has been under clinical investigation for more than 20 years 
(Cavazzana-Calvo et al., 2005, Engel et al., 2003) .  Clinical trials since the year 2000 have 
employed an approach that was first reported from two subjects treated in Milan, Italy and has 
recently been updated with 10 subjects (Aiuti et al., 2002, Aiuti et al., 2009).  This approach 
involves discontinuing Adagen® (in subjects receiving Adagen as an ERT) and administering 
non-myeloablative conditioning prior to the infusion of ADA vector-transduced autologous 
CD34+ stem cells.  In addition to the Milan study, variations on this protocol are currently 
under investigation in the UK, US, and Japan.  More than 40 affected individuals (most of 
whom had been receiving Adagen) have been treated at these centers (Aiuti et al., 2002, Aiuti 
et al., 2009, Candotti et al., 2012, Cappelli and Aiuti 2010, Engel et al., 2007, Gaspar et al., 
2006, Gaspar et al., 2013).  Reconstitution of immune function is generally slow and may take 
1 year or more.  In most (but not all) affected individuals, stable ADA expression in lymphoid 
cells has been achieved, along with correction of metabolic abnormalities in erythrocytes, 
which has resulted in maintenance of good health without the need for ERT.  In contrast to the 
experience with gene therapy for X-linked SCID, no subjects with ADA deficiency have thus 
far been reported to develop leukemia as a result of vector-associated insertional mutagenesis 
following gene therapy (Aiuti et al., 2007, Cappelli and Aiuti 2010).  However, because of this 
concern and in order to achieve more effective ADA expression, the clinical investigation of 
gene therapy using lentiviral vectors is now underway (Farinelli et al., 2014). 
5.2
Description of the Study Product
Revcovi is approved by the FDA for the treatment of ADA-SCID in pediatric and adult 
subjects.  Revcovi is a recombinant adenosine deaminase (rADA) based on bovine amino acid 
sequence, conjugated to monomethoxypolyethylene glycol (mPEG).  rADA is manufactured 
in E.coli and is covalently conjugated to mPEG with a succinimidyl carbamate (SC) linker to 
produce methoxypolyethylene glycol recombinant adenosine deaminase. The approximate 
molecular weight of Revcovi is 113 KDa.  
Revcovi was developed to replace the bovine-derived ADA in Adagen with recombinant ADA.  
Similar to Adagen, Revcovi provides an exogenous source of ADA enzyme that is associated 
with a decrease in toxic adenosine and deoxyadenosine nucleotides (dAXP) levels as well as 
an improvement in lymphocyte number and function.  
The polyethylene glycol (PEG) used for manufacturing Revcovi is similar to the PEG used to 
manufacture Adagen.  However, the succinimidyl succinate (SS) linker used to link PEG to 
ADA in Adagen has been replaced by the more stable SC linker in Revcovi. 
The enzyme used for manufacturing Revcovi is recombinant and based on the same sequence 
as Adagen.  Native bovine ADA undergoes post-transcriptional modification, with C-terminal 
processing (removal of the last six amino acids) and oxidation of cysteine at position 
74 (Cys74).  Therefore, rADA in SC-PEG rADA has been engineered so that the sequence 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 22 of 85
Date: 04th February 2022
encoding the last six amino acids of ADA have been deleted, and in addition, Cys74 has been 
mutated to serine (C74S), which reduces oxidative degradation of the molecule at this site 
without decreasing enzymatic activity of the protein.  
Replacing Adagen with Revcovi eliminates any risk of transmission of transmissible 
spongiform encephalopathy (TSE) or adventitious mammalian viruses (e.g. bovine spongiform 
encephalopathy) to patients as well as guarantees a more consistent, stable, and indefinite 
supply of drug for the ADA-SCID patient population.  Revcovi will also resolve the instability 
of Adagen (9-month shelf life) determined by the spontaneous dePEGylation during storage 
and protein degradation caused by the presence of protease impurities in the Adagen drug 
product.  Additional details for Revcovi are provided in the Revcovi Package Insert (PI). 
5.3
Product Background Information
Revcovi provides an exogenous source of ADA enzyme that is associated with a decrease in 
toxic adenosine and dAXP, thereby correcting the metabolic abnormalities and cellular toxicity 
associated with the absence of ADA.  This section provides a summary of nonclinical and 
clinical experience with Revcovi.  
Additional details are provided in the Revcovi PI.
5.3.1
Non-Clinical Experience 
The pharmacodynamic (PD), pharmacokinetic (PK), and toxicologic properties of Revcovi 
were evaluated in animal models [Leadiant Biosciences data on file].  Where appropriate, 
comparisons were made with Adagen.  The ability of the drug to generate antibodies that bind 
and neutralize Revcovi was studied together with the PK analysis.  
5.3.1.1 Pharmacology
ADA-/-mice were used to compare the efficacy of Adagen and Revcovi. ADA-/- mice were 
generated and genotyped.  ADA-/- mice were injected IM or intraperitoneally (IP) in several 
dosing regimens with selected doses of Adagen or Revcovi.  Compounds were given on the 
same schedule (once every 4 days × 5 starting on postnatal Day 1 until postnatal Day 21, and 
followed, if needed, once each week until postnatal Day 42) and at equivalent doses 
(5 U/mouse injected IM or IP).  Both untreated ADA+/+ and ADA-/- mice as well as ADA-/- 
mice treated with Revcovi or Adagen were sacrificed 18 days to 6 weeks following injection.  
Bronchial alveolar lavage fluid, thymus, and spleen were collected for the analysis of 
adenosine concentrations using reversed-phase high-performance liquid chromatography as 
well as for total cell counts and cellular differentials.  Blood was obtained from the circulation 
or thoracic cavity at the time of sacrifice to measure ADA enzymatic activity using zymogram 
or spectrophotometric analysis, respectively. Survival and body weight also were assessed.
Results of the pharmacology and PD studies performed in the ADA-/- mouse model suggest 
Revcovi behaves very similarly to Adagen and both compounds are highly effective.  
Consistent with this, when Adagen and Revcovi were given at equivalent doses and schedules, 
both PEG-ADA compounds 1) were delivered to the circulatory system with equal efficiency 
in both ADA+/+  and ADA-/-  mice; 2) increased ADA plasma levels to similar, clinically 
relevant levels; 3) decreased abnormally high adenosine levels found in the lung, spleen, or 
thymus to a similar extent; 4) maintained thymus and spleen cellularity, including total cell 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 23 of 85
Date: 04th February 2022
numbers and T- and B-cell populations; and 5) promoted the survival of ADA-/- mice.  There 
is a suggestion that Revcovi may be more efficacious than Adagen in the ADA-/- mouse model.  
The results tended to show Revcovi-treated ADA-/- mice having statistically lower adenosine 
levels in the thymus compared with Adagen, as well as a consistent trend toward better 
improvement of most PD endpoints (body weight, survival, and thymocyte and splenocyte cell 
number, as well as adenosine levels in spleen) when compared with Adagen.  These effects 
correlated with 35% higher plasma levels of ADA activity derived from Revcovi compared 
with Adagen when analyzed either 24 or 72 hours after the last dose; the higher plasma levels 
of ADA activity are likely due to the longer half-life of Revcovi.
5.3.1.2 Pharmacokinetics 
Revcovi demonstrated improved in vitro stability in human plasma in comparison with 
Adagen.  Two single-dose intravenous studies in rats were conducted.  In these studies, PK 
parameters for ADA activity were markedly increased for Revcovi as compared with 
unPEGylated Revcovi and were equivalent to or slightly different than those for Adagen 
(i.e., in one experiment, Revcovi had lower clearance, longer half-life, and higher area under 
the curve [AUC] compared to Adagen). 
Single IM doses of Revcovi or Adagen were given to rats or dogs at two dose levels (30 and 
150 U/kg).  AUC and maximum concentration (Cmax) values for ADA activity increased in 
proportion to dose for both rats and dogs.  The AUC values for Revcovi were statistically 
significantly higher (approximately 45% in rats, 55% in dogs) compared with Adagen.  
Terminal elimination half-lives (t1/2) also were increased approximately 30% in rats and 80% 
in dogs when Revcovi was compared with Adagen.  The calculated mean t1/2 in rats after a 
single dose was 49 to 61 hours for Revcovi and 36 to 50 hours for Adagen.  In dogs, these 
values were 128 to 154 hours for Revcovi and 68 to 79 hours for Adagen. 
In multiple-dose studies, Revcovi was given every 3 to 4 days for 4 weeks (total of 9 doses) at 
three dose levels (30, 100, and 300 U/kg).  These studies were conducted under Good 
Laboratory Practice (GLP) guidance.  AUC and Cmax values for ADA activity were higher on 
Day 29 as compared with Day 1 for rats that received 300 U/kg Revcovi and dogs that received 
30, 100, or 300 U/kg Revcovi.  In contrast, likely due to detectable anti-drug antibodies, 
marked reductions in Day 29 exposure values for ADA activity occurred for male rats that 
received 30 U/kg Revcovi or 30 U/kg Adagen, female rats that received 30 U/kg Revcovi, and 
male rats that received 100 U/kg Revcovi.  In dogs, Day 29 AUC values were markedly 
reduced for 1 of 5 males that received 30 U/kg Revcovi and 1 of 5 females that received 100 
U/kg Revcovi.  Anti-drug binding antibodies were present in the plasma of rats that received 
Revcovi or Adagen and in most dogs that received Revcovi at the end of the 4-week treatment 
periods and/or recovery periods.  In rare cases, neutralizing antibodies were detected that 
reduced the enzymatic activity of ADA in experimental assays. 
In conclusion, the PK (ADA activity) following single-dose IM administration to rats and dogs 
demonstrate that AUC and t1/2 were significantly higher for Revcovi compared to Adagen.  
Repeat doses of 30 U/kg Revcovi or 30 U/kg Adagen in rats, as well as 30 U/kg or 100 U/kg 
in dogs, resulted in the formation of anti-drug antibodies in some animals and markedly 
reduced exposure to ADA activity in comparison with single-dose administration. Despite the 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 24 of 85
Date: 04th February 2022
presence of anti-drug binding antibodies in rats and dogs in the repeat-dose studies, there was 
no evidence for clinical anaphylactic reactions to Revcovi or Adagen in either species.
5.3.1.3 Toxicology 
The single-dose studies of Revcovi and Adagen in rats and dogs were conducted primarily for 
PK assessment.  Revcovi and Adagen were dosed intramuscularly.  Toxicology evaluations 
including clinical signs, body weight, and food consumptions were done for up to 14 days after 
injection, after which animals were sacrificed.  The experiments were performed under non-
GLP conditions. 
The toxicity profile of Revcovi also was evaluated in Sprague-Dawley CD® rats and Beagle 
dogs in 4-week repeat-dose IM GLP toxicology studies. Animals were administered 30, 100, 
or 300 U/kg of Revcovi every 3 or 4 days for 4 weeks (9 doses total) with a 4-week recovery 
period.  Microscopic pathology evaluations were performed on approximately 
40 tissues/animals. 
Revcovi given IM was well tolerated in rats and dogs in single- and repeat-dose studies.  No 
mortality was observed in any of these studies, and no adverse effects on clinical condition, 
body weight, food consumption, electrocardiograms (dogs), or microscopic pathology were 
evident in either species at any dose.  Adagen was similarly well tolerated in rats and dogs at 
single doses of 30 and 150 U/kg and in rats at 30 U/kg given every 3 or 4 days for 4 weeks as 
part of a PK study. 
Compound-related findings were seen in the repeat-dose IM studies after 4 weeks of treatment 
(9 doses) and were limited to slight increases in mean platelet volume (MPV) values (3% to 
7%) for male rats that received 30, 100, or 300 U/kg Revcovi; slightly prolonged mean values 
for activated partial thromboplastin time (aPTT) for male and female rats that received 300 
U/kg Revcovi (5 to 6 seconds); slightly prolonged aPTT for male dogs that received 30, 100, 
and 300 U/kg Revcovi (6 to 20 seconds) and female dogs that received 100 and 300 U/kg 
Revcovi (8 and 14 seconds); and red foci at the injection sites for 2 of 10 male rats that received 
100 U/kg Revcovi.  The increased MPV and aPTT values were considered compound related 
but not adverse because of the small magnitude of change and lack of correlative changes.  
Partial or complete recovery was evident in both species for all of the changes after 4 weeks 
of recovery.  These clinical pathology changes could not be compared to effects associated 
with Adagen because Adagen was not administered in these studies. 
The no observed adverse effect levels (NOAELs) were the highest doses given in each of the 
IM studies, which were 150 U/kg Revcovi in the single-dose rat and dog studies and 300 U/kg 
Revcovi in the repeat-dose rat and dog studies.  Despite the presence of anti-drug binding 
antibodies, which were present in the rat plasma following repeated doses of Revcovi or 
Adagen and in most dogs that received repeated doses of Revcovi, no clinical observations 
were suggestive of an anaphylactoid response in any of the studies.  The Day 29 AUC0-∞ values 
at the NOAEL doses of 300 U/kg in the repeat-dose studies were 1.7- to 2.0-fold higher in rats 
and 3.2-fold higher in dogs than the corresponding Day 1 values. 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 25 of 85
Date: 04th February 2022
5.3.1.4 Conclusions 
The nonclinical data demonstrate that Revcovi was highly efficacious in a mouse knockout 
model that mimics human ADA-SCID.  In such ADA-deficient mice, compared with Adagen, 
Revcovi was at least as effective in its ability to: 

Increase ADA plasma levels to clinically relevant levels. 

Decrease abnormally high adenosine levels found in the lung, spleen or thymus to a 
similar extent. 

Maintain thymus and spleen cellularity, including total cell numbers and T- and B-cell 
populations.

Promote the survival of mice. 
Revcovi was well tolerated in rats and dogs at doses that are physiologically relevant.
5.3.2
Clinical Experience
Revcovi was administered intramuscularly in two prospective, open-label, single-arm, 
multicenter studies to evaluate efficacy, safety, tolerability, and PK in patients with 
ADA-SCID: STP-2279-002 (Study 1) was conducted in the United States and STM-279-301 
(Study 2) was conducted in Japan under Teijin Ltd., a Leadiant Biosciences partner. 
5.3.2.1 Study 1
Study 1, conducted in the US (NCT 01420627), is a Phase III, open-label multicenter, single-
arm, one-way crossover study of Revcovi, which has been completed.  The purpose of this 
clinical study is to evaluate the safety, efficacy, and PK of Revcovi in 6 subjects with ADA-
SCID, 4 males and 2 females, who are receiving therapy with Adagen.  The study treatment 
consists of three phases: Adagen Lead-in phase (minimum of 3 weeks), the Revcovi Treatment 
Phase (weeks 1 through 21), and a Revcovi Maintenance Phase.  Six subjects treated in the 
study were 8 to 37 years of age at the start of the study.  The starting weekly dose of Revcovi 
is calculated based on the last Adagen dose received in the study. Revcovi doses range from 
0.188 mg/kg to 0.292 mg/kg. The initial treatment for the 8 yr old was with a product that 
contained EDTA and resulted in significant pain at the injection site. That subject withdrew 
from the study and the product was reformulated without EDTA. Subsequently a total of 6 
subjects aged 16-37 were evaluated for efficacy and safety.
The efficacy endpoints assessed are: 1) trough dAXP Level (metabolic detoxification was 
defined as a trough erythrocyte dAXP concentration equal to or below 0.02 mmol/L), 2) trough 
plasma ADA activity (adequate trough plasma ADA activity is defined as trough plasma ADA 
activity equal to or above 15 mmol/hr/L), and 3) immune status (lymphocyte and B-, T-, and 
natural killer (NK)-lymphocyte subset counts as well as quantitative immunoglobulin [Ig] 
concentration [IgG, IgA, IgM]). A PK assessment was performed during Week 9 of the 
Revcovi Treatment phase. 
All six subjects reached the 21-week endpoint of the treatment phase, and 5 out of 6 subjects 
received treatment with Revcovi for over 135 weeks. These subjects (except for one value in 
a subject at treatment week 47) had erythrocyte dAXP concentration equal to or below 0.02 
mmol/L.  These subjects had trough plasma ADA activity equal to or above 15 mmol/hr/L at 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 26 of 85
Date: 04th February 2022
88/89 timepoints and maintained metabolic detoxification for at least 2 years under Revcovi 
treatment.  Subjects achieved trough plasma ADA activity above 30 mmol/hr/L by week 5, 
except for one subject who achieved this level at week 1.
Lymphocyte and subset counts during Revcovi treatment increased above levels observed 
during the Adagen Lead-in phase (i.e., PK day 1 or before the start of Revcovi treatment): 
maximum increases of approximately 3-fold at Weeks 60-73 for one subject, maximum 
increases of approximately 2- to 3-fold at Weeks 73-99 for one subject and approximately 1.5- 
to 3-fold for the third subject at several timepoints.  For the five subjects who completed the 
primary endpoint (21 weeks of treatment) and received Revcovi for over 135 weeks, a positive 
trend between high trough plasma ADA activity and increased total lymphocyte counts was 
observed. 
Observations for the other subject in the study, indicate that this subject also achieved complete 
detoxification based on trough dAXP and trough plasma ADA activity level, and showed stable 
or slightly increased lymphocyte counts during Revcovi treatment relative to values recorded 
during the Adagen lead-in phase.  
The most common adverse reactions were cough (3/6 subjects) and vomiting (2/6 subjects). 
Other adverse reactions that were reported in one subject each were: abdominal pain upper, 
arthralgia, asthenia, cerumen impaction, conjunctivitis, convulsion, dental caries, diarrhea, ear 
canal irritation, ear lobe infection, epistaxis, fatigue, fungal skin infection, gait disturbance, 
gastrointestinal infection, groin abscess, hematochezia, haemophilus infection (pulmonary), 
hemoptysis, influenza, injection site discomfort, laceration, lymphadenopathy, migraine, nasal 
edema, nausea, nephrolithiasis, oral candidiasis, oropharyngeal pain, otitis externa, productive 
cough, rash, stoma site infection, swelling face, tooth abscess, tooth extraction and upper 
respiratory tract infection, regardless of Investigator causality assessment.
5.3.2.2 Study 2
Study 2, conducted in Japan, is a single-arm clinical study that assessed the safety, efficacy 
and PK of Revcovi in subjects with ADA-SCID.  The study includes two phases: 1) Evaluation, 
consisting of a Dose Adjustment Period (5 weeks) and a Dose Maintenance Period (16 weeks); 
and 2) Continuous Administration (Extension) Phase, to be continued until the end of the study. 
A total of four subjects were enrolled in the study: two males (age 25 years and 3.4 months) 
and two females (age 16 years and 4.3 months).  Two subjects who were on Adagen treatment 
within four weeks before entering the study received a first dose of Revcovi that was calculated 
to be equivalent to the last Adagen dose received. One subject who did not receive Adagen 
within four weeks prior to entering the study was given the first dose of Revcovi at 0.1 mg/kg 
body weight, followed by second and third doses at 0.133 mg/kg body weight and weekly 
thereafter. Over the dose adjustment phase of the study, the dose was titrated to meet criteria 
for dAXP level (equal to or below 0.02 mmol/L) and adequate trough ADA activity (equal to 
or above 15 mmol/ hr/L). These 3 subjects received Revcovi for at least 21 weeks (having 
completed the 5-week Dosage Adjustment Period and the 16-week Dose Maintenance Period) 
before entering the Extension Period. The fourth subject (newly diagnosed Adagen-naïve 
subject with cytomegalovirus (CMV) pneumonia was dosed at a 0.4 mg/kg weekly (divided 
into twice a week administration) for 16 weeks. 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 27 of 85
Date: 04th February 2022
All 4 of the subjects in Study 2 achieved and maintained detoxification (trough dAXP 
[erythrocyte or blood] ≤ 0.02 mmol/L throughout their participation in the Treatment Phase of 
21 weeks (Evaluation Phase for Study 2).  Serum ADA activity increased after administering 
Revcovi for all four subjects, with three subjects achieving level over 15 mmol/hr/L during the 
Dose Maintenance period.  Total lymphocyte counts and B-/T-/NK-lymphocyte subset counts 
for three subjects increased from Screening to Day 15 during dose adjustment and were stable 
or increasing during the Dose Maintenance Period.
There were 22 reported adverse events (AEs) for four subjects.  The most common AEs were 
respiratory infections (2/4 subjects).  
5.4
Target Population and Study Rationale
Study CLI-06814AA1-01 is being performed as a post-marketing commitment following the 
approval of Revcovi by the FDA for the treatment of ADA-SCID in pediatric and adult 
patients.  The introduction of Revcovi is the first new product as an ERT in ADA-SCID 
patients since Adagen approval in 1990.  Revcovi is a PEGylated rADA that has been 
developed to replace the bovine-derived components in PEG-ADA (Adagen).  Similar to 
Adagen, Revcovi provides a specific and direct replacement of the ADA enzyme.  As for 
Adagen, the mechanism of action of Revcovi is to correct the metabolic abnormalities 
associated with adenosine accumulation due to the absence of ADA and to detoxify cells.  The 
purpose of the study is to bolster the established safety and efficacy data on Revcovi in patients 
with ADA-SCID and collect safety and efficacy data on patients started de novo ERT with 
Revcovi.
There are four types of patients with ADA-SCID who may be eligible for treatment with 
Revcovi, including:

Patients currently receiving chronic ERT with Adagen

Infants diagnosed via newborn screening and/or definitive testing for ADA deficiency

Patients preparing for HSCT or HSC-GT

Patients who decline, are ineligible or do not respond to HSCT or HSC-GT
5.5
Potential Risks and Benefits
Revcovi (elapegademase-lvlr) is approved by the FDA for the treatment of ADA-SCID in 
pediatric and adult patients.  Its safety and efficacy were established on the basis of two 
prospective studies.  Revcovi provides an exogenous source of ADA enzyme that is associated 
with a decrease in toxic adenosine and deoxyadenosine nucleotides levels as well as an 
improvement in lymphocyte number and function.  Information gathered will supplement the 
safety, tolerability and efficacy of Revcovi in post-approval use in patients with ADA-SCID.
Refer to the Revcovi PI for additional information.

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 28 of 85
Date: 04th February 2022
6
STUDY PURPOSE, OBJECTIVES AND ENDPOINTS
6.1
Purpose
The purpose of this clinical registry study is to bolster the established safety and efficacy data 
on Revcovi in patients with ADA-SCID and collect safety and efficacy data on patients started 
de novo ERT with Revcovi.  
6.2
Objectives
To conduct a registry study on patients with ADA-SCID treated with Revcovi and have 
periodic clinical and biochemical assessments for safety and dose adjustment based on ADA 
activity, erythrocyte dAXP levels and/or clinical assessment by the treating physician.
6.3
Endpoints
The procedures used to collect study data for the assessment of study endpoints are described 
in Section 10.
Biochemical assessments to adjust Revcovi dosing throughout the study include trough plasma 
ADA activity and RBC dAXP, which will be assessed from trough plasma samples obtained 
during the study as outlined in the Suggested Schedule of Assessments in Appendix 1 and 
Appendix 2.
Immune status (optional) will be analyzed throughout the study by the following (if assessed): 

absolute lymphocyte count

lymphocyte subset (B, T, and NK) analysis: the number of cells for each subset will be 
determined by fluorescence-activated cell sorter (FACS) using the following panel: 

CD3+ (Mature T cells) - Percent and Absolute

CD3+ CD8+ (Suppressor T Cells) - Percent and Absolute

CD3+ CD4+ (Helper Cells) - Percent and Absolute

CD (16+56) + (NK Cells) - Percent and Absolute

CD19+ (B Cells) - Percent and Absolute

Absolute Lymphocytes (CD45+)

%CD4 (Helper Cells)/%CD8 (Suppressor T Cells)

Quantitative immunoglobulin (Ig) concentration (IgG, IgA, IgM).

It is recommended that Investigators consider a measurement of immune response 
(PHA stimulation or equivalent)
Clinical status will be assessed through determination of the following:

Infections will be determined and defined as either: 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 29 of 85
Date: 04th February 2022

Clinically documented – subjects with documented signs and symptoms of infection 
without positive microbiologic cultures

Microbiologically documented – subjects with documented signs and symptoms of 
infection and with positive viral or bacterial cultures

Hospitalizations – incidence and duration of hospitalizations through completion of the 
study 

Growth – height, weight and growth curve determinations through completion of the 
study (Note: this assessment should be done for subjects < 18 years of age)

Overall survival through the end of the study

Quality of life will be assessed using the PedsQL Infant Scales (ages 1 to 12 months), 
PedsQL Infant Scales (ages 13 to 24 months), PedsQL 4.0 Toddler (2 to 4 years), 
PedsQL 4.0 Young Child Report (5 to 7 years), PedsQL 4.0 Child Report (8 to 
12 years), PedsQL 4.0 Teen Report (13 to 18 years), and for subjects older than 
18 years, the SF36 and the PADQOL.  Assessments for those under age 5 will be 
completed by the parent.  For children 5 to 18 years, the parent or health care provider 
will determine the ability of the subject to self-report. QOL assessment data will be 
collected from study participants via scripted phone calls by the study call center and 
QOL responses will be entered directly into the electronic data capture (EDC) system. 
QOL assessments will be collected prospectively for 24 months after starting Revcovi.
Safety will be assessed by determination of AEs, SAEs, clinical signs and symptoms from 
physical examination, and laboratory evaluations. 
A decrease of ADA activity below 30 mmol/hr/L from a previous acceptable level suggests an 
increase in weight requiring a dose increase adjustment, noncompliance to treatment or a 
development of antibodies (anti-drug, anti-PEG, and neutralizing antibodies).  Antibodies to 
Revcovi should be suspected if a persistent fall in pre-injection levels of trough plasma ADA 
activity below 15 mmol/hr/L occurs. In such subjects, testing for antibodies to Revcovi should 
be performed as is recommended in the Revcovi PI.
7
STUDY DESIGN
7.1
Overview of Study Design
Protocol CLI-06814AA1-01 is designed as a single-arm, open-label, multicenter registry study 
in patients with ADA-SCID requiring Revcovi as ERT.  The eligible study population includes 
adult subjects who are currently receiving chronic ERT with Adagen, infants diagnosed via 
newborn screening and definitive testing for ADA deficiency, patients preparing for HSCT or 
HSC-GT, and patients who decline, are ineligible or do not respond to HSCT or HSC-GT.
Subjects for whom written informed consent/assent is obtained will be assigned a number and 
undergo enrollment procedures.  The date of ICF signature is the date of enrollment into the 
registry. Subjects should have initial, trough erythrocyte dAXP levels and plasma ADA 
activity measurements collected prior to start of Revcovi as part of standard of care.  
Additionally, at enrollment, physical examination, vital signs, and laboratory values for total 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 30 of 85
Date: 04th February 2022
lymphocytes and subset analysis, as well as quantitative immunoglobulins, should be collected.  
Subjects who started treatment with Revcovi before enrollment into the  CLI-06814AA1-01 
study, should have data collected retrospectively in accordance with the Suggested Schedule 
of Assessments (Appendix 1 and Appendix 2) and in conformity to local standard of care 
practice.
Subjects should receive weekly IM dose(s) of Revcovi and will be followed throughout a 
period of at least 24-months according to the Suggested Schedule of Assessments (Appendix 
1 and Appendix 2).  Trough dAXP and ADA activity should be monitored throughout this 
treatment period, and AEs, immunogenicity, laboratory assessments, physical examination, 
and vital signs will also be assessed.  
All Phase III STP-2279-002 participants are permitted to enroll into the CLI-06814AA1-01 
registry at the time they discontinue from the Phase III STP-2279-002 study. Their first post-
baseline visit in the CLI-06814AA1-01registry will be Treatment Month 6. See the Suggested 
Schedule of Assessments (Appendix 1).  
 Enrolled subjects will be followed until the last enrolled patient has reached a minimum of 24 
months of Revcovi treatment or until undergoing HSCT or HSC-GT, whichever occurs first.  
Subjects undergoing HSCT or HSC-GT will be followed one month after the last Revcovi dose 
and again at six months to assess AEs and survival. 
Throughout the duration of the study, subjects will continually be assessed for AEs.  Immune 
status (lymphocyte subsets and quantitative immunoglobulins), clinical status (infections, 
hospitalization, growth, and overall survival) should also be assessed throughout the treatment 
period. QOL assessments will be prospectively collected for a maximum of 24 months after 
starting Revcovi.
A yearly review of AEs will be conducted by a Data Safety Monitoring Committee to identify 
any safety signals or trends.
7.2
Study Treatments
All subjects, including Adagen-naïve subjects and those previously treated with Adagen, 
should receive Revcovi according to dosing recommendations in the Revcovi PI.  Subjects 
who started Revcovi treatment prior to study enrollment should continue to be dosed in 
accordance with provider or Revcovi PI recommendations.  Study medication administration 
details are presented in Section 10.10.1.
7.3
Assignment of Subjects to Treatment
This is a non-randomized study. Each patient who is on treatment with Revcovi under 
commercial setting, meets all eligibility criteria and is accepted for study participation, will be 
assigned a unique subject number (see Section 10.2) and will have Adagen/Revcovi treatment 
information collected
7.4
Study Duration
Enrolled subjects will be followed until the last enrolled patient has reached 24 months of 
Revcovi treatment or until undergoing HSCT or HSCGT, whichever occurs first. Subjects 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 31 of 85
Date: 04th February 2022
undergoing HSCT or HSCGT will be followed one month and again at six months after final 
Revcovi dose to assess for AEs and survival.
7.5
Methods to Minimize Bias
Due to the single-arm, open-label study design, blinding is not necessary in this study. 
Laboratory assessments performed for clinical and dose adjustments are objective data 
provided by certified clinical laboratories and are not subject to bias.
7.6
Appropriateness of Study Measurements
In this study, data on Revcovi treatment should be monitored by measuring trough plasma 
ADA activity, trough dAXP levels, and total lymphocyte counts as recommended in the 
Revcovi PI.  Monitoring should be more frequent if therapy is interrupted or if an enhanced 
rate of clearance of plasma ADA activity develops. 
Safety in this study will be assessed by monitoring AEs, laboratory parameters (serum 
chemistry, hematology, and urinalysis), physical examination changes and vital signs.  These 
are standard assessments for monitoring safety in clinical trials.  In addition, monitoring of 
binding and neutralizing antibodies is commonly used to monitor patients treated with 
therapeutic biological products such as Adagen and Revcovi.
Other measurements include additional immune status markers (see Section 10.7), assessments 
of clinical status (incidence of infections, growth assessment, hospitalization incidence and 
duration, and survival) (see Section 10.8), and assessments of quality of life (see Section 10.9).  
These assessments are commonly used to monitor patients treated with Adagen.
7.7
Study Monitoring Committees
An independent Data and Safety Monitoring Committee (DSMC) will be set up to monitor the 
conduct of the study.  At minimum, the DSMC will review safety, ADA activity, and erythrocyte 
dAXP data on an annual basis. Chiesi PV will send notice via email to DSMC members regarding deaths, 
regardless of relatedness to Revcovi, along with associated MedWatch and any corresponding documentation. 
A Charter for the DSMC will be written as an independent document.
8
Revcovi
8.1
Description of Revcovi
Revcovi (elapegademase-lvlr) is rADA based on bovine amino acid sequence, conjugated to 
mPEG. rADA is manufactured in E.coli and is covalently conjugated to mPEG with a 
succinimidyl carbamate linker to produce methoxypolyethylene glycol recombinant adenosine 
deaminase (SC-PEG rADA). The approximate molecular weight of elapegademase-lvlr (SC-
PEG rADA) is 113 KDa. 
Revcovi (elapegademase-lvlr) injection is a sterile, preservative free, clear, colorless solution 
for IM use supplied in single-dose vials.  Each vial provides 1.5 mL of solution containing 
2.4 mg elapegademase-lvlr (1.6 mg/mL), sodium chloride (12.75 mg), sodium phosphate 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 32 of 85
Date: 04th February 2022
dibasic heptahydrate (12.7 mg), sodium phosphate monobasic monohydrate (3.81 mg), and 
Water for Injection, USP.  The pH is 6.9. 
Revcovi is manufactured by Leadiant Biosciences, however, Chiesi is reported on the 
commercial labels. 
8.2
Supply and Labeling 
Commercially available Revcovi will be used for this study and obtained by patients directly 
from a specialty pharmacy. Revcovi will not be provided to patients by the site staff or 
pharmacy.  Vials of commercially available Revcovi will be boxed individually and labeled in 
accordance with FDA requirements. 
8.3
Storage Conditions (See Revcovi PI)
Revcovi should be stored refrigerated at +2°C to +8ºC (36°F to 46°F).  Do not freeze.  Refer 
to the Revcovi PI
8.4
Preparation for Administration (See Revcovi PI)
Revcovi is to be administered in accordance with instructions in the Revcovi PI.
8.5
Procedure for Unblinding
Not applicable
8.6
Revcovi Accountability
As this is a registry study, drug accountability procedures are not applicable because subjects 
will be obtaining drug directly from a pharmacy or healthcare provider. 
9
STUDY POPULATION
9.1
Number of Subjects
The study will enroll all patients who meet all study entry criteria described in Sections 9.2 
and 9.3.  There are no restrictions on the number of subjects a single study center may enroll. 
9.2
Inclusion Criteria

Patients currently receiving chronic ERT with Adagen® and transitioned/transitioning 
to Revcovi;

Infants diagnosed via newborn screening and definitive testing for ADA deficiency 
prescribed Revcovi;

Patients receiving Revcovi while preparing for Hematopoietic Stem Cell Transplant 
(HSCT) or Hematopoietic Stem Cell Gene Therapy (HSCGT);

Patients who decline, are ineligible or do not respond to HSCT or HSC-GT and 
resume/start Revcovi.

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 33 of 85
Date: 04th February 2022
9.3
Exclusion Criteria

Any condition that, in the opinion of the Investigator, makes the patient unsuitable for 
the study.
9.4
Post-enrollment Restrictions
9.4.1
Concomitant Medications
There are no known drug interactions with Revcovi.  
9.4.2
Dietary Restrictions
There are no dietary restrictions for subjects enrolled in the study.
9.5
Withdrawal of Enrolled Subjects 
In the absence of a significant protocol violation, every effort will be made by the Investigator 
to keep subjects in the study.  The primary reason for a subject withdrawing prematurely should 
be selected from the following standard categories: 

AE – clinical or laboratory events that in the judgment of the Investigator require 
discontinuation of Revcovi in the best interests of subject. 

Death – death of the subject, whether study related or not.

Withdrawal of Consent – subject desires to withdraw from further participation in the 
study in the absence of a medical need to withdraw determined by the Investigator.

Lost to follow-up – the subject did not return for one or more follow-up visit(s) 
following the start of Revcovi treatment.

Subject meets withdrawal criteria – the subject’s condition meets the criteria for 
withdrawal from the study (Section 9.5.1).

Other – causes of premature termination from the study other than the above (e.g., 
termination of study by Chiesi Farmaceutici S.p.A., subject relocated).
9.5.1
Withdrawal Criteria
There is not mandated criteria for withdrawal other than treatment discontinuation. Reasons 
for subject withdrawal or completion of the maintenance period may include the following:

AE requiring the discontinuation of Revcovi treatment

Death

Loss to follow-up

Withdrawal of consent

Investigator’s decision, e.g., Investigator believes it is no longer in the subject’s best 
interest to remain in the study

Study completion 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 34 of 85
Date: 04th February 2022

Other reason - causes of premature termination from the study other than the above 
(e.g., subject relocated) 
The reason for study discontinuation should be documented in the subject’s source documents 
and in the electronic case report form (eCRF). 
Subjects are free to withdraw from the study at any time for any reason.  
The reasons for subject withdrawal or study completion, as well as details relevant to the 
subject withdrawal or study completion, shall be recorded in the eCRF.  Subjects withdrawn 
before their completion of the study will undergo all procedures scheduled for study 
completion as outlined in Section 11.3. 
Any subject withdrawn due to any AE (whether serious or non-serious) or clinically significant 
abnormal laboratory test values will be evaluated by the Investigator or his/her designee, or a 
monitoring physician, and will be treated and/or followed up until the symptoms or values 
return to normal or acceptable levels, as judged by the Investigator. 
9.5.2
Withdrawal Procedures
Under any circumstance, a final physical examination of each subject must be performed at the 
time of study discontinuation.  See Section 11.3 for procedures related to the discontinuation 
or the end of the study.
Should a subject be withdrawn from the study, all efforts will be made to complete and report 
the observations as thoroughly as possible, including a complete final evaluation at the time of 
the subject’s withdrawal with an explanation of the reason subject was withdrawn from the 
study.
9.5.3
Replacement of Discontinued Subjects
Subjects who do not complete the study will not be replaced. 
10
DESCRIPTION OF STUDY PROCEDURES AND VARIABLES
10.1 Informed Consent
Patients or the legally authorized representative of eligible patients who express interest in 
participating in the study must sign an Institutional Review Board (IRB)/Independent Ethics 
Committee (IEC)-approved Informed Consent Form that conforms to the Elements of the 
Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule Authorization (see 
Sections 14.3.2 and 14.3.3) before initiation of any study activities.  Documentation of consent 
must be completed by the Investigator or his/her designee. 
The Investigator and other members of the study site’s treating team will review the nature of 
the study, its purpose, the procedures involved, the expected duration, the potential risks and 
benefits, and alternative therapies including best supportive care.  Patients must be informed 
that participation in the study is voluntary, he/she may withdraw from the study at any time, 
and withdrawal from the study will not affect his/her subsequent medical treatment or 
relationship with the treating physician.  Patients will also be informed of any financial costs 
that the patient will or may incur as a result of participation in the study, and that their study 
record and medical records/documents that pertain directly to the study will be reviewed and 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 35 of 85
Date: 04th February 2022
possibly copied by Chiesi or its designee, or a governmental agency (such as the FDA), and 
that every effort will be made to maintain patient confidentiality. 
The Informed Consent must be witnessed and dated by the Investigator or his/her designee, 
and the original retained by the Investigator/Study Site as part of the subject’s study record. 
For subjects under 18 years of age, Assent of the minor child must be obtained in accordance 
with Good Clinical Practices (GCP) and the requirements of the reviewing IRB/IEC. 
A copy of the fully executed/signed Informed Consent Form and Assent Form (if applicable) 
must be given to the subject. In the event the subject is re-screened, the subject is not required 
to sign another Informed Consent form unless the subject is re-screened more than 30 days 
from the previous Informed Consent form’s signature date.
10.2 Screening and Enrollment
The Investigator or his/her designee will obtain a signed Informed Consent and Assent (if 
required) before initiating any study-specific procedures.  Each subject that is consented will 
be given a 3-digit sequential subject number, beginning with 001 at each study site. The date 
of ICF signature is considered the date of enrollment into the registry. 
10.3 History and Baseline Characteristics
The following history and demographic data will be collected:

Demographics – age, gender, race, and ethnicity

Disease background and history: 
-
Date of diagnosis
-
Prior treatments for severe combined immunodeficiency, including dates 
and results
-
History of hospitalizations and infectious complications over the past year
-
Other significant disease-related medical history

Medical History – in addition to the disease background and history, a complete 
evaluation of history of disorders of the following systems – cardiovascular, 
pulmonary, gastrointestinal, urologic, hematologic, neurologic, ophthalmologic, 
otolaryngeal, musculoskeletal, endocrine, and psychosocial. Note:  any medications 
being taken for active conditions should be included in the medication history, while 
prior surgical procedures and allergies to medications, including medication and 
reaction should be included in the medical history.

Medication History – all prescription and non-prescription medications (including 
blood products, use of vitamins, supplements and herbal remedies) taken since the first 
dose of Revcovi will be recorded.  Information recorded includes the medication name, 
dose, dose regimen, route of administration, start and stop (if applicable) dates, and 
indication for use.  Note: if a product is being taken for the prevention of a condition, 
“prophylaxis for” or “prevention of” should be included in the description of indication. 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 36 of 85
Date: 04th February 2022
10.4 Maximum Total Blood Collection Volume 
During the study participation, the maximum amounts of venous blood that will be collected 
are listed in Sections 10.5.3 and 10.5.4. Whenever possible, microtainers should be used for 
pediatric subjects. 
10.5 Safety Procedures
10.5.1
Physical Examination
Physical examination will be performed in accordance with the Investigator’s standard of care, 
including an examination of general appearance, skin, neck (including thyroid), eyes, ears, 
nose, throat, lungs, heart, abdomen, back, lymph nodes, extremities, and nervous system. 
Height and weight (must be in kg) should be collected as part of the physical examination. 
A physical examination should be performed as indicated in the Suggested Schedules of 
Assessments as shown in Appendix 1 and Appendix 2.
Changes in physical examination findings (e.g., new findings, changes in status of previous 
findings) should be documented.  Findings made after the start of Revcovi administration that 
meet the definition of an AE (see Section 12.2.1) should be recorded on the Adverse Event 
CRF.
10.5.2
Vital Signs
Vital signs should include sitting systolic and diastolic blood pressure, pulse rate, respirations, 
and temperature. Clinically meaningful changes in vital signs made after the start of Revcovi, 
which meet the definition of an AE, should be recorded on the Adverse Event CRF.
10.5.3
Safety Laboratory Assessments
The following safety laboratory evaluations are not required per protocol but may be performed 
by the site’s local laboratory in accordance with the Investigator’s standard of care.

Hematology:  Hemoglobin, hematocrit, white blood count, differential (includes at 
least: neutrophils [include bands], lymphocytes, monocytes, eosinophils, and 
basophils), and platelet count.

Serum chemistry: Bicarbonate, blood urea nitrogen, calcium, chloride, creatinine, 
glucose, magnesium, phosphate, potassium, sodium, and total protein, albumin, 
alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and total 
bilirubin.

Urinalysis: Macroscopic (bilirubin, blood, glucose, ketones, leukocyte esterase, nitrite, 
pH, protein, specific gravity, and urobilinogen). Microscopic examination will include 
red blood cells, white blood cells, bacteria, and casts.
The safety laboratory assessment results, if available, will be included in the eCRF for the 
study. 
Following the start of study treatment clinically meaningful laboratory abnormalities will be 
reported as AEs.

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 37 of 85
Date: 04th February 2022
10.5.4
Immunogenicity
Immunogenicity should be assessed in accordance with the Revcovi PI.  If testing is necessary, 
venous blood samples for determination of anti-Revcovi binding and neutralizing antibodies, 
and anti-PEG antibodies will be collected in 2-mL ethylenediaminetetraacetic acid (EDTA) 
tubes. 
Once treatment with Revcovi has been initiated, a target trough plasma ADA activity level 
should be at least 30 mmol/hr/L.  A decrease of ADA activity below this level suggests 
inadequate weight-based dosing, administration noncompliance or a development of 
antibodies (anti-drug, anti-PEG, and neutralizing antibodies).  Antibody development to 
Revcovi should be suspected if a persistent fall in pre-injection levels of trough plasma ADA 
activity to below 15 mmol/hr/L occurs, and testing for antibodies to Revcovi should be 
performed. 
10.5.5
Adverse Event Assessment
All AEs whether observed by the Investigator or his/her designee, elicited by the Investigator 
or his/her designee (e.g., via physical examination findings or review of laboratory results), or 
spontaneously reported by the subject will be documented in the subject’s medical 
record/chart. 
Subjects should be assessed for any change in interval health status including any AEs.  For 
each AE the following information will be recorded in the medical record/chart:

Onset date 

Resolution date 

Serious or non-serious (see Section 12.2.3)

Relationship to Revcovi (see Section 12.2.4)

Severity/intensity (see Section 12.2.5)

Actions taken to manage/treat the event

Outcome of the event—resolved, resolved with sequalae, ongoing, death 
All AEs should be followed until they are resolved or until a stable clinical endpoint is reached. 
Any SAEs assessed by the investigator as causally related (i.e. “possibly”, “probably” or 
“definitely” related) to the administration of Revcovi should be reported to Chiesi US PV 
(please see Section 12 for complete information on SAE reporting). 
Any subject withdrawn due to any AE (whether serious or non-serious) or clinically significant 
abnormal laboratory test value will be evaluated by the Investigator or his/her designee, or a 
monitoring physician, and will be treated and/or followed up until the symptom(s) or value(s) 
return to normal/Baseline or acceptable levels, as judged by the Investigator.  

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 38 of 85
Date: 04th February 2022
10.6 Biochemical Variables for Dose Adjustments and Efficacy
10.6.1
Trough Plasma ADA Activity
Venous blood samples for the determination of ADA activity should be collected in a 2-mL 
EDTA collection tube (or as otherwise specified by the testing laboratory) in accordance with 
recommendations in the Revcovi PI.   
10.6.2
Erythrocyte dAXP
Venous blood samples for the determination of total erythrocyte dAXP (EDTA tube, 2 mL per 
timepoint) should be collected in accordance with recommendations in the Revcovi PI.  
Samples will be collected, processed, and shipped to the laboratory for analysis. Samples for 
dAXP can be assessed in the same 2-ml sample for ADA (Note: this should be confirmed with 
the laboratory). 
10.7 Immune Status 
10.7.1
Lymphocyte Subset Analysis 
Blood samples for lymphocyte subset analysis should be done in accordance with provider-
based standards and consistent with the PI recommendations as described below. 
Samples will be collected, processed, and shipped to the laboratory for analysis according to 
each sites’ standards of care.  

CD3+ (Mature T cells): Percent and Absolute 

CD3+ CD8+ (Suppressor T Cells): Percent and Absolute 

CD3+ CD4+ (Helper Cells): Percent and Absolute 

CD (16+56) + (Natural Killer Cells): Percent and Absolute 

CD19+ (B Cells): Percent and Absolute

Absolute Lymphocytes (CD45+) 

%CD4 (Helper Cells) / %CD8 (Suppressor T Cells) 

Quantitative Immunoglobulins (IgG, IgA, IgM)
10.7.2
Immune Function analysis
Blood for assessments of Immune function according to provider standards (PHA stimulation, 
pneumococcal vaccine response, flow cytometry, etc.) should be done as deemed clinically 
necessary by the provider and recorded in the CRF
10.8 Clinical Status 
10.8.1
Infections 
Subjects suspected of having an infection should have signs and symptoms of the suspected 
infection evaluated.  Appropriate cultures should be obtained based upon clinical presentation. 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 39 of 85
Date: 04th February 2022
All infections will be classified by the Investigator as clinically or microbiologically 
documented as described below: 

Clinically documented – subjects with documented signs and symptoms of infection 
without positive cultures 

Microbiologically documented – subjects with documented signs and symptoms of 
infection and with positive cultures 
10.8.2
Hospitalizations
All hospitalizations assessed by the investigator as causally related (i.e. “possibly”, “probably” 
or “definitely” related) to the administration of Revcovi should be reported to Chiesi US PV 
(please see Section 12 for complete information on SAE reporting).  
10.8.3
Growth
For subjects younger than 18 years, height (in cm) and weight (in kg) should be obtained for 
determination of height-for-age and weight- for-age Z-scores. 
10.8.4
Overall Survival
Subject survival will be recorded throughout the subject’s participation in the study.   If death 
is reported during the study, the date of death and reason for the subject death should be 
documented and recorded. 
All subject deaths should be reported immediately (see Section 12.4) to Chiesi US PV.
10.9 Quality of Life
Age-based health-related quality of life assessments will be made using PedsQL scales for 
subjects aged 1 to 12 months (infants), 13 to 24 months (infants), 2 to 4 years (toddlers), 5 to 
7 years (young children), 8 to 12 years (children), and 13 to 18 years (teens); for subjects over 
18 years, the SF-36 and PADQOL will be administered. Assessments for subjects under age 5 
will be completed by the parent.   For subjects from 5 to 18 years old, parents and heath care 
providers will determine the ability of the subject to self-report. However, parental consent and 
attendance is required during the call. QOL assessment data will be collected prospectively for 
a maximum of 24 months after starting Revcovi from study participants via scripted phone 
calls by the study call center and QOL responses will be entered directly into the electronic 
data capture (EDC) system. These assessments will be conducted utilizing the schedule 
outlined in section 11.2 below, independent of clinic evaluations to minimize data collection 
requirements of the study sites. 
10.10 Revcovi Administration and Compliance 
10.10.1
Dosage and Administration
Beginning at the Enrollment Visit, subjects transitioning from Adagen to Revcovi and Adagen-
naïve subjects (newborn) should be dosed in accordance with the Revcovi PI recommendation.  
Subjects who started Revcovi treatment prior to study enrollment should continue to be dosed 
in accordance with provider or Revcovi PI recommendation.

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 40 of 85
Date: 04th February 2022
Subjects transitioning from Adagen to Revcovi:  Trough ADA activity and dAXP levels should 
be assessed prior to transition.  
For subjects currently receiving Adagen at ≤ 30 U/kg/wk or an unknown Adagen dose, the 
starting weekly IM dose with Revcovi is 0.2 mg/kg.  The weekly dose may be increased by 
increments of 0.033 mg/kg weekly if trough ADA activity is under 30 mmol/hr/L, dAXP is 
above 0.02 mmol/L, and/or the immune reconstitution is inadequate based on the clinical 
assessment of the subject.  
For subjects currently receiving Adagen at > 30 U/kg/wk, an equivalent Revcovi dose (mg/kg) 
can be calculated using the following equation:
The total weekly dose may be divided and administered in multiple IM injections per week.  
The weekly Revcovi dose may be increased by increments of 0.033 mg/kg weekly if trough 
ADA activity is under 30 mmol/hr/L, dAXP is above 0.02 mmol/L, and/or the immune 
reconstitution is inadequate based on the clinical assessment of the subject. 
Adagen-naïve subjects: The starting weekly IM dose with Revcovi is 0.4 mg/kg of ideal body 
weight, divided into two weekly doses, for a minimum of 12 to 24 weeks until immune 
reconstitution is achieved based on clinical assessment by the treating physician.  The dose 
may be gradually adjusted down to maintain trough ADA activity over 30 mmol/hr/L, dAXP 
under 0.02 mmol/L, and to maintain adequate immune reconstitution based on clinical 
assessment of the subject by the treating physician.
10.10.2
Dose Adjustments
Adjustments of the dose and/or schedule of Revcovi may be required if a subject’s trough 
plasma ADA activity is less than 30 μmol/h/mL, trough dAXP level is greater than 
0.02 μmol/mL, or immune reconstitution is inadequate based on clinical assessment of the 
subject by Investigator’s determination. 
The optimal long-term dose and schedule of administration should be established by a 
physician for each subject individually and may be adjusted based on the laboratory values for 
trough ADA activity, trough erythrocyte dAXP level, and on the treating physician’s medical 
assessment of the subject’s clinical status (see Revcovi PI).
10.10.3
Treatment Delays
Revcovi should be administered in accordance with the Suggested Schedules of Assessments 
for Adagen-transitioning and Adagen-naïve subjects (Appendix 1 and Appendix 2, 
respectively).  The Investigator, upon consultation with Chiesi Farmaceutici S.p.A. and the 
Investigator, may elect to delay or withhold a dose if the clinical condition of the subject 
warrants such action. 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 41 of 85
Date: 04th February 2022
10.10.4
Assessment of Revcovi Compliance
Subjects will often be self-administering drug from commercially available inventories. 
Dosing dates, times and volumes will be captured via subject-reported diaries/medication 
administration forms. Diaries/medication administration forms will be monitored as part of 
medication compliance.
10.11 Assessment of Concomitant Medications of Interest
The use of concomitant medications of interest, including ADA inhibitors and Ig replacement 
therapy, should be recorded at each visit.  Concomitant medications of interest are all anti-
infectives that are administered after the first dose of Revcovi, regardless of when they were 
started. If applicable, the name of the medication, total daily dose, route of administration, and 
start and stop dates should be documented.
10.12 Protocol Adherence 
This study is conducted in accordance the principles of the Declaration of Helsinki, the 
International Council for Harmonisation Guidance on GCP and the requirements of federal 
and local regulatory authorities regarding the conduct of clinical trials and the protection of 
human subjects.  
The Investigator and the study personnel will recommend subject adherence with the study 
requirements, procedures and suggested schedule of events.  The Investigator or a licensed 
physician Sub-Investigator listed on Form FDA 1572 or equivalent, is present for initial dose 
administration of Revcovi at the Enrollment Visit and for the post-dose monitoring and 
evaluation for all subjects.  The Investigator or physician sub-Investigator will be available by 
phone/pager at all other times throughout the study for the management of the subjects enrolled 
in this clinical trial.  Deviations from any study evaluations/procedures is documented in the 
subject’s source documents and CRFs and reported to the Sponsor and IRB/IEC as required.
11
SCHEDULE OF STUDY PROCEDURES
A schedule of suggested study procedures for subjects transitioning from Adagen to Revcovi 
is shown in Appendix 1 and for Adagen-naïve subjects in Appendix 2.  
11.1 Enrollment
Subjects who fulfill all of the inclusion criteria and none of the exclusion criteria may be 
enrolled into the study. The date of ICF signature is the date of enrollment into the registry.
The following evaluations should be performed or collected retrospectively (if available) 
before starting Revcovi unless otherwise indicated. 

Informed assent/consent

Demographics

Medical history and baseline characteristics (including ADA-mutation results, if 
available)

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 42 of 85
Date: 04th February 2022

Assessment of infectious complications and hospitalizations within the past 12 months

Concomitant medications/procedures

Physical examination (including height and weight) from 1 year prior to start of 
Revcovi treatment

Vital signs 

Safety laboratory assessments: hematology, serum chemistry, urinalysis (if available)

Immune Function (if available)

B-/T-/NK-lymphocyte subset

Trough plasma ADA activity and erythrocyte dAXP

Quantitative immunoglobulins

Immune Function analyses (response to PHA, pneumococcal vaccine or equivalent)

Immunogenicity – Revcovi antibody titers (i.e., neutralizing and binding antibodies) 
and anti-PEG antibodies (only if indicated)

Quality of Life assessments
11.2 Revcovi Treatment Period  
The assessments and schedule described in the following subsections are suggested based on 
recommendations described in the Revcovi PI.  
Monitoring for trough plasma ADA activity and trough erythrocyte dAXP levels is essential 
to establish therapeutic levels of Revcovi and to maintain detoxification.  The schedule of 
monitoring listed in the PI and in this protocol are recommended and not required.  Clinicians 
should individualize the schedule of monitoring to assess the effect of Revcovi on trough 
plasma activity of ADA, erythrocyte dAXP, and immune function (lymphocyte counts, 
lymphocyte subsets and immune response) while balancing the risk of phlebotomy and subject 
visit burden.  The listing for the schedule of assessments (Appendix 1 and Appendix 2) 
provides a template for reporting of monitoring and is not a rigid requirement.
Safety laboratory assessments should be collected, if available, but these assessments are not 
required (Section 10.5.3). Immunogenicity testing should also be performed, if indicated, in 
accordance with the Revcovi PI (see Section 10.5.4).  
With the exception of ADA and dAXP assessments, a microtainer should be used for blood 
collection for subjects younger than 10 years of age whenever possible.
11.2.1
Adagen-transitioning subjects 
Visit frequency is determined by Provider/Subject as needed for clinical standard of care with 
recommendations in the Prescribing information.

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 43 of 85
Date: 04th February 2022
11.2.1.1
Treatment Week 4
At Treatment Week 4 (± 1 week), the subject should return to the study site and have the 
following procedures performed as per suggested schedule of assessments: 

AE assessment

Concomitant medications

Revcovi dosing and compliance

Assessment of infectious complications and hospitalizations

Assessment of concomitant use of ADA inhibitors and Ig replacement therapy and any 
procedures performed since last study visit

Vital signs 

Physical examination (including height and weight)

Safety Laboratory assessments (if available)

Immunogenicity
Blood samples should be obtained prior to administration of Revcovi for: 

Trough plasma ADA activity
11.2.1.2
Treatment Week 8
At Treatment Week 8 (± 1 week), the subject should return to the study site and have the 
following procedures performed as per suggested schedule of assessments: 

AE assessment

Concomitant medications

Revcovi dosing and compliance

Assessment of infectious complications and hospitalizations

Assessment of concomitant use of ADA inhibitors and Ig replacement therapy and any 
procedures performed since last study visit

Vital signs 

Physical examination (including height and weight)

Safety Laboratory assessments (if available)

Immunogenicity
Blood samples should be obtained prior to administration of Revcovi for: 

Trough erythrocyte dAXP 
Trough plasma ADA activity

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 44 of 85
Date: 04th February 2022
11.2.1.3
Treatment Week 12 
At Treatment Week 12 (±1 week), the subject should return to the study site and have the 
following procedures performed as per suggested schedule of assessments, if needed: 

AE assessment

Concomitant medications

Revcovi dosing and compliance

Assessment of infectious complications and hospitalizations

Assessment of concomitant use of ADA inhibitors and Ig replacement therapy and any 
procedures performed since last study visit

Vital signs 

Physical examination (including height and weight)

Safety Laboratory assessments (if available)

Immunogenicity

QOL will be assessed using the PedsQL Infant Scales (ages 1 to 12 months), PedsQL 
Infant Scales (ages 13 to 24 months), PedsQL 4.0 Toddler (2 to 4 years), PedsQL 4.0 
Young Child Report (5 to 7 years), PedsQL 4.0 Child Report (8 to 12 years), 
PedsQL 4.0 Teen Report (13 to 18 years), and for subjects older than 18 years, the 
SF36 and the PADQOL.  Assessments for those under age 5 will be completed by the 
parent.  For children 5 to 18 years, the parent or health care provider will determine the 
ability of the subject to selfreport. QOL assessment data will be collected from study 
participants via scripted phone calls by the study call center and QOL responses will 
be entered directly into the EDC system. QOL assessments will be collected 
prospectively for 24 months after starting Revcovi.
Blood samples should be obtained prior to administration of Revcovi for: 

Trough plasma ADA activity

B-/T-/NK-lymphocyte subset
11.2.1.4
Treatment Month 6
At Treatment Month 6 (± 3 weeks), the subject should return to the study site and have the 
following procedures performed as per suggested schedule of assessments: 

AE assessment

Concomitant medications

Revcovi dosing and compliance

Assessment of infectious complications and hospitalizations

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 45 of 85
Date: 04th February 2022

Assessment of concomitant use of ADA inhibitors and Ig replacement therapy and any 
procedures performed since last study visit

Vital signs 

Physical examination (including height and weight)

Safety Laboratory assessments (if available)

Immunogenicity

Quality of life will be assessed using the PedsQL Infant Scales (ages 1 to 12 months), 
PedsQL Infant Scales (ages 13 to 24 months), PedsQL 4.0 Toddler (2 to 4 years), 
PedsQL 4.0 Young Child Report (5 to 7 years), PedsQL 4.0 Child Report (8 to 
12 years), PedsQL 4.0 Teen Report (13 to 18 years), and for subjects older than 
18 years, the SF36 and the PADQOL.  Assessments for those under age 5 will be 
completed by the parent.  For children 5 to 18 years, the parent or health care provider 
will determine the ability of the subject to selfreport. QOL assessment data will be 
collected from study participants via scripted phone calls by the study call center and 
QOL responses will be entered directly into the EDC system. QOL assessments will be 
collected prospectively for 24 months after starting Revcovi.
Blood samples should be obtained prior to administration of Revcovi for: 

Trough plasma ADA activity

B-/T-/NK-lymphocyte subset

Quantitative immunoglobulins
11.2.1.5
Treatment Month 9 
At Treatment Month 9 (± 3 weeks), the subject should return to the study site and have the 
following procedures performed as per suggested schedule of assessments: 

AE assessment

Concomitant medications

Revcovi dosing and compliance

Assessment of infectious complications and hospitalizations

Assessment of concomitant use of ADA inhibitors and Ig replacement therapy and any 
procedures performed since last study visit

Vital signs 

Physical examination (including height and weight)

Safety Laboratory assessments (if available) 

Immunogenicity

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 46 of 85
Date: 04th February 2022

Quality of life will be assessed using the PedsQL Infant Scales (ages 1 to 12 months), 
PedsQL Infant Scales (ages 13 to 24 months), PedsQL 4.0 Toddler (2 to 4 years), 
PedsQL 4.0 Young Child Report (5 to 7 years), PedsQL 4.0 Child Report (8 to 
12 years), PedsQL 4.0 Teen Report (13 to 18 years), and for subjects older than 
18 years, the SF36 and the PADQOL.  Assessments for those under age 5 will be 
completed by the parent.  For children 5 to 18 years, the parent or health care provider 
will determine the ability of the subject to selfreport. QOL assessment data will be 
collected from study participants via scripted phone calls by the study call center and 
QOL responses will be entered directly into the EDC system
Blood samples should be obtained prior to administration of Revcovi for: 

Trough plasma ADA activity

B-/T-/NK-lymphocyte subset
11.2.1.6
Treatment Month 12
At Treatment Month 12 (± 3 weeks), the subject should return to the study site and have the 
following procedures performed as per suggested schedule of assessments: 

AE assessment

Concomitant medications

Revcovi dosing and compliance

Assessment of infectious complications and hospitalizations

Assessment of concomitant use of ADA inhibitors and Ig replacement therapy and any 
procedures performed since last study visit

Vital signs 

Physical examination (including height and weight)

Safety Laboratory assessments (if available) 

Immunogenicity

Quality of life will be assessed using the PedsQL Infant Scales (ages 1 to 12 months), 
PedsQL Infant Scales (ages 13 to 24 months), PedsQL 4.0 Toddler (2 to 4 years), 
PedsQL 4.0 Young Child Report (5 to 7 years), PedsQL 4.0 Child Report (8 to 
12 years), PedsQL 4.0 Teen Report (13 to 18 years), and for subjects older than 
18 years, the SF36 and the PADQOL.  Assessments for those under age 5 will be 
completed by the parent.  For children 5 to 18 years, the parent or health care provider 
will determine the ability of the subject to selfreport. QOL assessment data will be 
collected from study participants via scripted phone calls by the study call center and 
QOL responses will be entered directly into the EDC system. QOL assessments will be 
collected prospectively for 24 months after starting Revcovi.
Blood samples should be obtained prior to administration of Revcovi for: 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 47 of 85
Date: 04th February 2022

Trough plasma ADA activity

B-/T-/NK-lymphocyte subset

Quantitative immunoglobulins
11.2.1.7
 Treatment Month 15 
At Treatment Month 15 (± 3 weeks), the subject should return to the study site and have the 
following procedures performed as per suggested schedule of assessments: 

AE assessment

Concomitant medications

Revcovi dosing and compliance

Assessment of infectious complications and hospitalizations

Assessment of concomitant use of ADA inhibitors and Ig replacement therapy and any 
procedures performed since last study visit

Vital signs 

Physical examination (including height and weight)

Safety Laboratory assessments (if available) 

Immunogenicity
Blood samples should be obtained prior to administration of Revcovi for: 

Trough plasma ADA activity

B-/T-/NK-lymphocyte subset
11.2.1.8
Treatment Month 18
At Treatment Month 18 (± 3 weeks), the subject should return to the study site and have the 
following procedures performed as per suggested schedule of assessments: 

AE assessment

Concomitant medications

Revcovi dosing and compliance

Assessment of infectious complications and hospitalizations

Assessment of concomitant use of ADA inhibitors and Ig replacement therapy and any 
procedures performed since last study visit

Vital signs 

Physical examination (including height and weight)

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 48 of 85
Date: 04th February 2022

Quality of life will be assessed using the PedsQL Infant Scales (ages 1 to 12 months), 
PedsQL Infant Scales (ages 13 to 24 months), PedsQL 4.0 Toddler (2 to 4 years), 
PedsQL 4.0 Young Child Report (5 to 7 years), PedsQL 4.0 Child Report (8 to 
12 years), PedsQL 4.0 Teen Report (13 to 18 years), and for subjects older than 
18 years, the SF36 and the PADQOL.  Assessments for those under age 5 will be 
completed by the parent.  For children 5 to 18 years, the parent or health care provider 
will determine the ability of the subject to selfreport. QOL assessment data will be 
collected from study participants via scripted phone calls by the study call center and 
QOL responses will be entered directly into the EDC system. QOL assessments will be 
collected prospectively for 24 months after starting Revcovi.

Safety Laboratory assessments (if available) 

Immunogenicity
Blood samples should be obtained prior to administration of Revcovi for: 

Trough erythrocyte dAXP

Trough plasma ADA activity

B-/T-/NK-lymphocyte subset

Quantitative immunoglobulins
11.2.1.9
Treatment Month 21 
At Treatment Month 21 (± 3 weeks), the subject should return to the study site and have the 
following procedures performed as per suggested schedule of assessments: 

AE assessment

Concomitant medications

Revcovi dosing and compliance

Assessment of infectious complications and hospitalizations

Assessment of concomitant use of ADA inhibitors and Ig replacement therapy and any 
procedures performed since last study visit

Vital signs 

Physical examination (including height and weight)

Safety Laboratory assessments (if available) 

Immunogenicity
Blood samples should be obtained prior to administration of Revcovi for: 

Trough plasma ADA activity

B-/T-/NK-lymphocyte subset

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 49 of 85
Date: 04th February 2022
11.2.1.10
 Treatment Month 24 
At Treatment Month 24 (± 3 weeks), the subject should return to the study site and have the 
following procedures performed as per suggested schedule of assessments: 

AE assessment

Concomitant medications

Revcovi dosing and compliance

Assessment of infectious complications and hospitalizations

Assessment of concomitant use of ADA inhibitors and Ig replacement therapy and any 
procedures performed since last study visit

Vital signs 

Physical examination (including height and weight)

Quality of life will be assessed using the PedsQL Infant Scales (ages 1 to 12 months), 
PedsQL Infant Scales (ages 13 to 24 months), PedsQL 4.0 Toddler (2 to 4 years), 
PedsQL 4.0 Young Child Report (5 to 7 years), PedsQL 4.0 Child Report (8 to 
12 years), PedsQL 4.0 Teen Report (13 to 18 years), and for subjects older than 
18 years, the SF36 and the PADQOL.  Assessments for those under age 5 will be 
completed by the parent.  For children 5 to 18 years, the parent or health care provider 
will determine the ability of the subject to selfreport. QOL assessment data will be 
collected from study participants via scripted phone calls by the study call center and 
QOL responses will be entered directly into the EDC system. QOL assessments will be 
collected prospectively for 24 months after starting Revcovi. 

Safety Laboratory assessments (if available) 

Immunogenicity
Blood samples should be obtained prior to administration of Revcovi for: 

Trough plasma ADA activity

B-/T-/NK-lymphocyte subset

Trough erythrocyte dAXP levels

Quantitative immunoglobulins (IgA, IgG, IgM)
11.2.1.11
Treatment Month 27+
Subjects should continue to return to study site every 3 months ± 3 weeks until the last enrolled 
patient has reached 24 months of treatment. The following procedures should be performed as 
per suggested schedule of assessments:

AE assessment

Concomitant medications

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 50 of 85
Date: 04th February 2022

Revcovi dosing and compliance

Assessment of infectious complications and hospitalizations

Assessment of concomitant use of ADA inhibitors and Ig replacement therapy and any 
procedures performed since last study visit

Vital signs 

Physical examination (including height and weight)

Safety Laboratory assessments (if available) 

Immunogenicity

Trough plasma ADA activity

B-/T-/NK-lymphocyte subset

Trough erythrocyte dAXP levels*

Quantitative immunoglobulins (IgA, IgG, IgM)*
Blood samples should be obtained prior to administration of Revcovi. Please refer to schedule of 
assessments for applicable blood draws per treatment visit. 
*  to be performed at every other visit (M30, 36, 42...), please refer to appendix 1 schedule of 
assessments
11.2.2
Adagen-naïve subjects 
Visit frequency is determined by Provider/Subject as needed for clinical standard of care with 
recommendations in the Prescribing information
11.2.2.1
Treatment Week 2
At Treatment Week 2 (± 3 days), the subject should return to the study site and have the 
following procedures performed as per suggested schedule of assessments: 

AE assessment

Concomitant medications

Revcovi dosing and compliance

Assessment of infectious complications and hospitalizations

Assessment of concomitant use of ADA inhibitors and Ig replacement therapy and any 
procedures performed since last study visit

Vital signs 

Physical examination (including height and weight)

Safety Laboratory assessments (if available) 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 51 of 85
Date: 04th February 2022

Immunogenicity
Blood samples should be obtained prior to administration of Revcovi for: 

Trough erythrocyte dAXP

Trough plasma ADA activity
11.2.2.2
Treatment Week 4
At Treatment Week 4 (± 3 days), the subject should return to the study site and have the 
following procedures performed as per suggested schedule of assessments: 

AE assessment

Concomitant medications

Revcovi dosing and compliance

Assessment of infectious complications and hospitalizations

Assessment of concomitant use of ADA inhibitors and Ig replacement therapy and any 
procedures performed since last study visit

Vital signs 

Physical examination (including height and weight)

Safety Laboratory assessments (if available) 

Immunogenicity
Blood samples should be obtained prior to administration of Revcovi for: 

Trough erythrocyte dAXP

Trough plasma ADA activity

B-/T-/NK-lymphocyte subset

Quantitative immunoglobulins
11.2.2.3
Treatment Week 6
At Treatment Week 6 (± 3 days), the subject should return to the study site and have the 
following procedures performed as per suggested schedule of assessments: 

AE assessment

Concomitant medications

Revcovi dosing and compliance

Assessment of infectious complications and hospitalizations

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 52 of 85
Date: 04th February 2022

Assessment of concomitant use of ADA inhibitors and Ig replacement therapy and any 
procedures performed since last study visit

Vital signs 

Physical examination (including height and weight)

Safety Laboratory assessments (if available) 

Immunogenicity
Blood samples should be obtained prior to administration of Revcovi for: 

Trough erythrocyte dAXP

Trough plasma ADA activity
11.2.2.4
Treatment Week 8
At Treatment Week 8 (± 3 days), the subject should return to the study site and have the 
following procedures performed as per suggested schedule of assessments: 

AE assessment

Concomitant medications

Revcovi dosing and compliance

Assessment of infectious complications and hospitalizations

Assessment of concomitant use of ADA inhibitors and Ig replacement therapy and any 
procedures performed since last study visit

Vital signs 

Physical examination (including height and weight)

Safety Laboratory assessments (if available) 

Immunogenicity
Blood samples should be obtained prior to administration of Revcovi for: 

Trough erythrocyte dAXP

Trough plasma ADA activity

B-/T-/NK-lymphocyte subset

Quantitative immunoglobulins
11.2.2.5
Treatment Week 10 
At Treatment Week 10 (± 3 days), the subject should return to the study site and have the 
following procedures performed as per suggested schedule of assessments: 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 53 of 85
Date: 04th February 2022

AE assessment

Concomitant medications

Revcovi dosing and compliance

Assessment of infectious complications and hospitalizations

Assessment of concomitant use of ADA inhibitors and Ig replacement therapy and any 
procedures performed since last study visit

Vital signs 

Physical examination (including height and weight)

Safety Laboratory assessments (if available) 

Immunogenicity
Blood samples should be obtained prior to administration of Revcovi for: 

Trough erythrocyte dAXP

Trough plasma ADA activity
11.2.2.6
Treatment Week 12
At Treatment Week 12 (± 3 days), the subject should return to the study site and have the 
following procedures performed as per suggested schedule of assessments: 

AE assessment

Concomitant medications

Revcovi dosing and compliance

Assessment of infectious complications and hospitalizations

Assessment of concomitant use of ADA inhibitors and Ig replacement therapy and any 
procedures performed since last study visit

Vital signs 

Physical examination (including height and weight)

Safety Laboratory assessments (if available) 

Immunogenicity

Quality of life will be assessed using the PedsQL Infant Scales (ages 1 to 12 months), 
PedsQL Infant Scales (ages 13 to 24 months), PedsQL 4.0 Toddler (2 to 4 years), 
PedsQL 4.0 Young Child Report (5 to 7 years), PedsQL 4.0 Child Report (8 to 
12 years), PedsQL 4.0 Teen Report (13 to 18 years), and for subjects older than 
18 years, the SF36 and the PADQOL.  Assessments for those under age 5 will be 
completed by the parent.  For children 5 to 18 years, the parent or health care provider 
will determine the ability of the subject to selfreport. QOL assessment data will be 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 54 of 85
Date: 04th February 2022
collected from study participants via scripted phone calls by the study call center and 
QOL responses will be entered directly into the EDC system. QOL assessments will be 
collected prospectively for 24 months after starting Revcovi.
Blood samples should be obtained prior to administration of Revcovi for: 

Trough erythrocyte dAXP

Trough plasma ADA activity

B-/T-/NK-lymphocyte subset

Quantitative immunoglobulins
11.2.2.7
Treatment Month 4 
At Treatment Month 4 (± 1 week), the subject should return to the study site and have the 
following procedures performed as per suggested schedule of assessments: 

AE assessment

Concomitant medications

Revcovi dosing and compliance

Assessment of infectious complications and hospitalizations

Assessment of concomitant use of ADA inhibitors and Ig replacement therapy and any 
procedures performed since last study visit

Vital signs 

Physical examination (including height and weight)

Safety Laboratory assessments (if available) 

Immunogenicity
Blood samples should be obtained prior to administration of Revcovi for: 

B-/T-/NK-lymphocyte subset
11.2.2.8
Treatment Month 5 
At Treatment Month 5 (± 1 week), the subject should return to the study site and have the 
following procedures performed as per suggested schedule of assessments: 

AE assessment

Concomitant medications

Revcovi dosing and compliance

Assessment of infectious complications and hospitalizations

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 55 of 85
Date: 04th February 2022

Assessment of concomitant use of ADA inhibitors and Ig replacement therapy and any 
procedures performed since last study visit

Vital signs 

Physical examination (including height and weight)

Safety Laboratory assessments (if available) 

Immunogenicity
Blood samples should be obtained prior to administration of Revcovi for: 

B-/T-/NK-lymphocyte subset
11.2.2.9
Treatment Month 6
At Treatment Month 6 (± 1 week), the subject should return to the study site and have the 
following procedures performed as per suggested schedule of assessments: 

AE assessment

Concomitant medications

Revcovi dosing and compliance

Assessment of infectious complications and hospitalizations

Assessment of concomitant use of ADA inhibitors and Ig replacement therapy and any 
procedures performed since last study visit

Vital signs 

Physical examination (including height and weight) 

Quality of life will be assessed using the PedsQL Infant Scales (ages 1 to 12 months), 
PedsQL Infant Scales (ages 13 to 24 months), PedsQL 4.0 Toddler (2 to 4 years), 
PedsQL 4.0 Young Child Report (5 to 7 years), PedsQL 4.0 Child Report (8 to 
12 years), PedsQL 4.0 Teen Report (13 to 18 years), and for subjects older than 
18 years, the SF36 and the PADQOL.  Assessments for those under age 5 will be 
completed by the parent.  For children 5 to 18 years, the parent or health care provider 
will determine the ability of the subject to selfreport. QOL assessment data will be 
collected from study participants via scripted phone calls by the study call center and 
QOL responses will be entered directly into the EDC system.  QOL assessments will 
be collected prospectively for 24 months after starting Revcovi.

Safety Laboratory assessments (if available) 

Immunogenicity
Blood samples should be obtained prior to administration of Revcovi for: 

Trough plasma ADA activity

B-/T-/NK-lymphocyte subset

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 56 of 85
Date: 04th February 2022

Quantitative immunoglobulins
11.2.2.10
Treatment Month 7 
At Treatment Month 7 (± 1 week), the subject should return to the study site and have the 
following procedures performed as per suggested schedule of assessments: 

AE assessment

Concomitant medications

Revcovi dosing and compliance

Assessment of infectious complications and hospitalizations

Assessment of concomitant use of ADA inhibitors and Ig replacement therapy and any 
procedures performed since last study visit

Vital signs 

Physical examination (including height and weight)

Safety Laboratory assessments (if available) 

Immunogenicity
Blood samples should be obtained prior to administration of Revcovi for: 

B-/T-/NK-lymphocyte subset
11.2.2.11
Treatment Month 8 
At Treatment Month 8 (± 1 week), the subject should return to the study site and have the 
following procedures performed as per suggested schedule of assessments: 

AE assessment

Concomitant medications

Revcovi dosing and compliance

Assessment of infectious complications and hospitalizations

Assessment of concomitant use of ADA inhibitors and Ig replacement therapy and any 
procedures performed since last study visit

Vital signs 

Physical examination (including height and weight)

Safety Laboratory assessments (if available) 

Immunogenicity
Blood samples should be obtained prior to administration of Revcovi for: 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 57 of 85
Date: 04th February 2022

Trough dAXP

B-/T-/NK-lymphocyte subset
11.2.2.12
Treatment Month 9 
At Treatment Month 9 (± 1 week), the subject should return to the study site and have the 
following procedures performed as per suggested schedule of assessments: 

AE assessment

Concomitant medications

Revcovi dosing and compliance

Assessment of infectious complications and hospitalizations

Assessment of concomitant use of ADA inhibitors and Ig replacement therapy and any 
procedures performed since last study visit

Vital signs 

Physical examination (including height and weight) 

Safety Laboratory assessments (if available) 

Immunogenicity

Quality of life will be assessed using the PedsQL Infant Scales (ages 1 to 12 months), 
PedsQL Infant Scales (ages 13 to 24 months), PedsQL 4.0 Toddler (2 to 4 years), 
PedsQL 4.0 Young Child Report (5 to 7 years), PedsQL 4.0 Child Report (8 to 
12 years), PedsQL 4.0 Teen Report (13 to 18 years), and for subjects older than 
18 years, the SF36 and the PADQOL.  Assessments for those under age 5 will be 
completed by the parent.  For children 5 to 18 years, the parent or health care provider 
will determine the ability of the subject to self-report. QOL assessment data will be 
collected from study participants via scripted phone calls by the study call center and 
QOL responses will be entered directly into the EDC system. QOL assessments will be 
collected prospectively for 24 months after starting Revcovi.
Blood samples should be obtained prior to administration of Revcovi for: 

Trough plasma ADA activity

B-/T-/NK-lymphocyte subset
11.2.2.13
Treatment Month 12
At Treatment Month 12 (± 3 weeks), the subject should return to the study site and have the 
following procedures performed as per suggested schedule of assessments: 

AE assessment

Concomitant medications

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 58 of 85
Date: 04th February 2022

Revcovi dosing and compliance

Assessment of infectious complications and hospitalizations

Assessment of concomitant use of ADA inhibitors and Ig replacement therapy and any 
procedures performed since last study visit

Vital signs 

Physical examination (including height and weight)

Quality of life will be assessed using the PedsQL Infant Scales (ages 1 to 12 months), 
PedsQL Infant Scales (ages 13 to 24 months), PedsQL 4.0 Toddler (2 to 4 years), 
PedsQL 4.0 Young Child Report (5 to 7 years), PedsQL 4.0 Child Report (8 to 
12 years), PedsQL 4.0 Teen Report (13 to 18 years), and for subjects older than 
18 years, the SF36 and the PADQOL.  Assessments for those under age 5 will be 
completed by the parent.  For children 5 to 18 years, the parent or health care provider 
will determine the ability of the subject to selfreport. QOL assessment data will be 
collected from study participants via scripted phone calls by the study call center and 
QOL responses will be entered directly into the EDC system. QOL assessments will be 
collected prospectively for 24 months after starting Revcovi.

Safety Laboratory assessments (if available) 

Immunogenicity
Blood samples should be obtained prior to administration of Revcovi for: 

Trough erythrocyte dAXP

Trough plasma ADA activity

B-/T-/NK-lymphocyte subset

Quantitative immunoglobulins
11.2.2.14
Treatment Month 15 
At Treatment Month 15 (± 3 weeks), the subject should return to the study site and have the 
following procedures performed as per suggested schedule of assessments: 

AE assessment

Concomitant medications

Revcovi dosing and compliance

Assessment of infectious complications and hospitalizations

Assessment of concomitant use of ADA inhibitors and Ig replacement therapy and any 
procedures performed since last study visit

Vital signs 

Physical examination (including height and weight)

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 59 of 85
Date: 04th February 2022

Safety Laboratory assessments (if available) 

Immunogenicity
Blood samples should be obtained prior to administration of Revcovi for: 

Trough plasma ADA activity

B-/T-/NK-lymphocyte subset
11.2.2.15
Treatment Month 18
At Treatment Month 18 (± 3 weeks), the subject should return to the study site and have the 
following procedures performed as per suggested schedule of assessments: 

AE assessment

Concomitant medications

Revcovi dosing and compliance

Assessment of infectious complications and hospitalizations

Assessment of concomitant use of ADA inhibitors and Ig replacement therapy and any 
procedures performed since last study visit

Vital signs 

Physical examination (including height and weight)

Assessment of Quality of Life (All subjects up to 18 years old will be assessed using 
the age specific PedsQL.  Parents or health care providers will determine the ability of 
subjects from 5 to 18 years to self-report.  Subjects over 18 years will be assessed using 
the SF 36 and PADQOL.) QOL assessment data will be collected from study 
participants via scripted phone calls by the study call center and QOL responses will 
be entered directly into the EDC system. QOL assessments will be collected 
prospectively for 24 months after starting Revcovi.

Safety Laboratory assessments (if available) 

Immunogenicity
Blood samples should be obtained prior to administration of Revcovi for: 

Trough erythrocyte dAXP

Trough plasma ADA activity

B-/T-/NK-lymphocyte subset

Quantitative immunoglobulins

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 60 of 85
Date: 04th February 2022
11.2.2.16
Treatment Month 21
At Treatment Month 21 (± 3 weeks), the subject should return to the study site and have the 
following procedures performed as per suggested schedule of assessments: 

AE assessment

Concomitant medications

Revcovi dosing and compliance

Assessment of infectious complications and hospitalizations

Assessment of concomitant use of ADA inhibitors and Ig replacement therapy and any 
procedures performed since last study visit

Vital signs 

Physical examination (including height and weight)

Safety Laboratory assessments (if available) 

Immunogenicity
Blood samples should be obtained prior to administration of Revcovi for: 

Trough plasma ADA activity

B-/T-/NK-lymphocyte subset
11.2.2.17
Treatment Month 24  
At Treatment Month 24 (± 3 weeks), the subject should return to the study site and have the 
following procedures performed as per suggested schedule of assessments: 

AE assessment

Concomitant medications

Revcovi dosing and compliance

Assessment of infectious complications and hospitalizations

Assessment of concomitant use of ADA inhibitors and Ig replacement therapy and any 
procedures performed since last study visit

Vital signs 

Physical examination (including height and weight)

Assessment of Quality of Life (All subjects up to 18 years old will be assessed using 
the age specific PedsQL.  Parents or health care providers will determine the ability of 
subjects from 5 to 18 years to self-report.  Subjects over 18 years will be assessed using 
the SF 36 and PADQOL.) QOL assessment data will be collected from study 
participants via scripted phone calls by the study call center and QOL responses will 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 61 of 85
Date: 04th February 2022
be entered directly into the EDC system. QOL assessments will be collected 
prospectively for 24 months after starting Revcovi. 

Safety Laboratory assessments (if available) 

Immunogenicity
Blood samples should be obtained prior to administration of Revcovi for: 

Trough erythrocyte dAXP

Trough plasma ADA activity

B-/T-/NK-lymphocyte subset

Quantitative immunoglobulins
11.2.2.18
Treatment Month 27+
Subjects should continue to return to study site every 3 months ± 3 weeks until the last enrolled 
patient has reached 24 months of treatment. The following procedures should be performed as 
per suggested schedule of assessments:

AE assessment

Concomitant medications

Revcovi dosing and compliance

Assessment of infectious complications and hospitalizations

Assessment of concomitant use of ADA inhibitors and Ig replacement therapy and any 
procedures performed since last study visit

Vital signs 

Physical examination (including height and weight)

Safety Laboratory assessments (if available) 

Immunogenicity

Trough erythrocyte dAXP*

Trough plasma ADA activity

B-/T-/NK-lymphocyte subset

Quantitative immunoglobulins*
Blood samples should be obtained prior to administration of Revcovi. Please refer to schedule 
of assessments for applicable blood draws per treatment visit. 
*  to be performed at every other visit (M30, 36, 42...), please refer to appendix 2 schedule of 
assessments

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 62 of 85
Date: 04th February 2022
11.3 Study Completion 
Study completion will be once the last patient enrolled has reached 24 months of Revcovi 
treatment  or until undergoing HSCT or HSCGT, whichever occurs first. The subject should 
return to the study site and have the following procedures performed as per suggested schedule 
of assessments: 

AE assessment

Assessment of infectious complications and hospitalizations

Assessment of concomitant use of ADA inhibitors and Ig replacement therapy and any 
procedures performed since last study visit

Assessment of Quality of Life (only performed during the first 24 months of starting on 
Revcovi)

Vital signs 

Physical examination (including height and weight)
Blood samples should be obtained for: 

Trough erythrocyte dAXP

Trough plasma ADA activity

B-/T-/NK-lymphocyte subset

Quantitative immunoglobulins

Safety laboratory assessments: hematology, serum chemistry, urinalysis (if available)
All subjects, regardless of the reason for study withdrawal (see Section 9.5.1), subjects should 
have the above evaluations performed, whenever possible.  All reasons for discontinuation of 
treatment must be documented.
12
ADVERSE EVENTS
12.1 Assessment Period
AEs are assessed from the time the subject receives their initial dose of Revcovi during the CLI-
06814AA1-01 registry through 4 weeks following the last dose. Subjects undergoing HSCT or 
HSCGT will be followed one month and again at 6 months after last Revcovi dose to assess AEs 
and survival. 
12.2 Definitions
12.2.1
Adverse Event
An AE is any untoward medical occurrence associated with the use of a drug in humans, 
whether or not considered drug related.  An AE can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding, for example), symptom, or disease 
temporally associated with the use of a drug and does not imply any judgment about causality.

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 63 of 85
Date: 04th February 2022
An untoward medical event which occurs outside the period of follow-up as defined in the 
protocol is not considered an AE.  Worsening of a medical condition for which the efficacy of 
the drug is being evaluated is not considered an AE.  
12.2.2
Unexpected Adverse Event
An adverse reaction is unexpected if the nature or severity of the event is not consistent with 
the applicable product information.  An unexpected AE is one that is not listed in the PI or is 
not listed at the specificity or severity that has been observed. 
For example, under this definition, hepatic necrosis would be unexpected (by virtue of greater 
severity) if the PI referred only to elevated hepatic enzymes or hepatitis. Similarly, cerebral 
thromboembolism and cerebral vasculitis would be unexpected (by virtue of greater 
specificity) if the package insert listed only cerebral vascular accidents. 
“Unexpected,” as used in this definition, also refers to AEs or suspected adverse reactions that 
are mentioned in the PI as occurring with a class of drugs or as anticipated from the 
pharmacological properties of the drug but are not specifically mentioned as occurring with 
the particular drug under investigation.
12.2.3
Serious Adverse Event
A serious adverse event (SAE) is an AE that in the view of either the Investigator or Sponsor, 
it results in any of the following outcomes: 

Death

Is life-threatening (an event that in the view of either the Investigator or Sponsor, its 
occurrence places the subject at immediate risk of death; it does not include an event 
that had it occurred in a more severe form, might have caused death.)

Requires in-subject hospitalization or prolongation of existing hospitalization

Results in persistent or significant disability/incapacity or substantial disruption of the 
ability to conduct normal life functions

Is a congenital anomaly or birth defect

Is another important medical event that may not be immediately life-threatening or 
result in death or hospitalization but, based upon appropriate medical judgment, may 
jeopardize the subject or may require medical or surgical intervention to prevent one 
of the other outcomes listed above.  Examples of such events are intensive treatment in 
an emergency room for allergic bronchospasm; blood dyscrasias or convulsions that do 
not result in hospitalization; or development of drug dependency or drug abuse.
The term “severe” is often used to describe the intensity (severity) of an event; the event 
itself may be of relatively minor medical significance (such as a severe headache).  This is 
not the same as “serious”, which is based on subject/event outcome or action criteria usually 
associated with events that pose a threat to a subject’s life or functioning.
12.2.4
Relationship to Revcovi 
The Investigator must attempt to determine if an AE is in some way related to the use of the 
Revcovi.  This relationship should be described based upon the following definitions:

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 64 of 85
Date: 04th February 2022

Unrelated: The AE is clearly due to causes distinct from the use of the Revcovi, such 
as a documented pre-existing condition, the subject’s clinical state, environmental 
factors, or the effect of other concomitant medications or treatments administered.

Unlikely: The AE does not follow a reasonable temporal sequence from administration 
of Revcovi, does not follow a known response pattern to Revcovi, and could readily 
have been due to other causes such as the subject’s clinical state, environmental factors, 
or the effect of other concomitant medications or treatments administered.

Possible:  The AE follows a reasonable temporal sequence from administration of 
Revcovi and follows a known response pattern to Revcovi, BUT, the AE could readily 
have been produced by the subject’s clinical state, environmental factors, or the effect 
of other concomitant medications or treatments administered.

Probable: The AE follows a reasonable temporal sequence from administration of 
Revcovi and follows a known response pattern to Revcovi, AND cannot be reasonably 
explained by the subject’s clinical state, environmental factors, or the effect of other 
concomitant medications or treatments administered.  The event improves upon 
discontinuation of Revcovi.

Definite:  The AE follows a reasonable temporal sequence from administration of 
Revcovi and follows a known response pattern to Revcovi.  Based on the known 
pharmacology of the study drug, the event is clearly related to the effect of the study 
drug.  The AE improves upon discontinuation of Revcovi and reappears upon repeat 
exposure.  Please use Definite if the causal association is considered “Certain”. 
12.2.5
Severity (Intensity) 
The Investigator assesses the severity (intensity) of all AEs according to the 
following grading system:

Grade 1 – (Mild AE) awareness of the event but is easily tolerated

Grade 2 – (Moderate AE) interferes with activities of daily living

Grade 3 – (Severe AE) incapacitating and causes inability to perform activities 
of daily living
12.3 Reporting of Adverse Events
All new events related to Revcovi, as well as those that worsen in intensity or frequency 
relative to baseline, which occur must be captured.  The Investigator or his/her staff should 
elicit information regarding the occurrence of AEs through information volunteered by the 
subject, open-ended questioning of the subject, physical examination results and review of 
laboratory results.  
Information recorded for each AE includes:
A medical diagnosis of the event (if a medical diagnosis cannot be determined, a 
description of each sign or symptom characterizing the event should be recorded) 
The date and time of onset of the event 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 65 of 85
Date: 04th February 2022
The date and time of resolution of the event 
Assessments of seriousness, causal relationship, and severity of the AE (see 
definitions in Sections 12.2.3, 12.2.4, 12.2.5, respectively)
o
For the purposes of SAE Reporting, adverse events assigned one of the 
following causality assessments by the investigator are considered causally 
related to the administration of Revcovi: 

Possible

Probable

Definite – (Please use Definite if the causal association is considered 
“Certain”)
Action(s) taken (if any) for management of the AE, including but not limited to change 
in Revcovi administration (e.g., temporary interruption in dosing, dose reduction); drug 
treatment; non-drug treatment; diagnostic procedures performed
Outcome of the AE: recovered; recovering; recovered with sequelae; event ongoing or 
not recovered; death 
All AEs are followed as medically appropriate until an outcome is determined as stated 
above.  
12.4 Reporting of Serious Adverse Events
All AEs and SAEs assessed by the investigator as causally related (i.e. “possibly”, 
“probably” or “definitely” related) to the administration of Revcovi should be reported by 
sending 
AE/SAE 
report 
form 
to 
Chiesi 
US 
Pharmacovigilance 
(PV) 
at 
us.medical@chiesi.com.  
12.5 Reporting of Pregnancy
Adequate and well-controlled studies with Revcovi have not been conducted in pregnant 
women to inform a drug-associated risk.  Animal reproduction studies have not been conducted 
with Revcovi.  No pregnancy was reported for any subjects receiving Revcovi.  It is not known 
whether Revcovi can cause fetal harm when administered to a pregnant woman or can affect 
reproduction capacity.  
If a female subject becomes pregnant or is found to be pregnant while on the study or a female 
partner of a male subject becomes pregnant during the study, the Chiesi Pharmacovigilance 
should be contacted immediately.  Although pregnancy is not a SAE, all pregnancies occurring 
during this study should be reported to Chiesi within 24 hours of becoming aware of the 
pregnancy and complete and submit a pregnancy report form. 
All pregnancies will be followed until delivery or pregnancy termination for maternal 
outcomes and at 1 month, 2 months, and 1 year for fetal outcomes. 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 66 of 85
Date: 04th February 2022
13
STATISTICS
13.1 Sample Size Determination
No formal sample size is calculated. The study will be open to enroll all eligible patients over 
a minimum of 2 years.
13.2 Statistical Methodology
13.2.1
Level of Significance
No hypothesis test will be done.
13.2.2
Analysis Populations 
The as-treated population, defined as all subjects who are enrolled and receive at least one dose 
of Revcovi, will be the primary analysis set in all analyses.
13.2.3
Data Analysis
Statistical analysis will be conducted by Chiesi, or its designee.  Analysis of study data will be 
performed after the last subject has completed assessments for the Treatment Month 24 Visit 
or, in the case of subject undergoing HSCT or HSC-GT, the 6 -month follow-up visit.  
Statistical analyses will be performed using Statistical Analysis Systems® (SAS®) 
Version 9.4 or later (SAS Institute, Cary, NC), or comparable software. 
A complete description of data handling rules and planned statistical analyses is detailed in a 
separate Statistical Analysis Plan. Unless otherwise specified in this document or in the 
Statistical Analysis Plan, baseline is defined as the last measurement for a variable before the 
initial dose of Revcovi, and missing data will generally not be imputed. Baseline for the 
patients transitioning from the Phase III STP-2279-002 study is the last available non-missing 
value prior to the initiation of Revcovi in the STP-2279-002 study. 
Analyses will be descriptive, with data listings, graphical presentations, frequency tabulations, 
and summary statistics as appropriate. 
Each subject will serve as his/her own control based on the baseline assessment of each 
endpoint as appropriate, including changes in body weight as percentile on the growth curve, 
antibody formation, etc.
Exposure and safety summaries will be presented by whether or not they previously 
participated in study STP-2279-002.
Additional statistical analyses, other than those described in this section, may be performed if 
deemed appropriate to further explore the study data.

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 67 of 85
Date: 04th February 2022
13.2.3.1
Study Conduct and Subject Disposition
The number of subjects treated will be tabulated.  Subjects not meeting the eligibility criteria 
will be documented.  Protocol violations will be reviewed.  Subjects who withdraw from the 
study will also be summarized using descriptive statistics by reason for withdrawal.   
13.2.3.2
Demographics and Baseline Characteristics 
Subject demographic data, baseline characteristics, and disease background at study entry will 
be summarized. Continuous variables will be summarized using descriptive statistics, 
including mean, standard deviation, median, and range. Categorical variables will be 
summarized in frequency tables. Missing categories will be presented if applicable.
For subjects younger than 18 years, growth curve percentiles for height, weight, and BMI will 
also be calculated and summarized. Missing categories will be presented if applicable.
Medical history at study entry will be listed but not summarized.
13.2.3.3
Revcovi Administration
Revcovi administration will be summarized starting from the enrollment in the CLI-
06814AA1-01 registry.  The total number of doses administered; the median (range) of doses 
administered; the median (range) treatment duration; dose modifications, dose delays, and dose 
omissions; and reasons for deviations from planned therapy will be described.
Exposure summaries will be presented by whether or not they previously participated in study 
STP-2279-002.
  
13.2.3.4
Biochemical Endpoint and Immune Status Analysis
Analyses of the following biochemical endpoints used for adjusting Revcovi dosing will be 
primarily descriptive, with data listings, graphical presentations, frequency tabulations, and 
summary statistics at each time point, as appropriate. 

Total erythrocyte dAXP from a trough blood sample 

Trough plasma ADA activity 

Immune function status, including:

Absolute Lymphocyte count 

B-, T-, and NK-lymphocyte subset analysis: the number of cells for each subset will be 
determined by FACS. The following subsets will be assessed: 

CD3+ (Mature T cells) - Percent and Absolute

CD3+ CD8+ (Suppressor T Cells) - Percent and Absolute 

CD3+ CD4+ (Helper Cells) - Percent and Absolute 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 68 of 85
Date: 04th February 2022

CD (16+56) + (Natural Killer Cells) - Percent and Absolute

CD19+ (B Cells) - Percent and Absolute 

Absolute Lymphocytes (CD45+)

%CD4 (Helper Cells) / %CD8 (Suppressor T Cells) 

Quantitative immunoglobulin concentration (IgA, IgG, IgM) 

Immune function measurement, if indicated (PHA stimulation or equivalent)
13.2.3.5
Safety Data Analysis 
Safety summaries will be presented by whether or not they previously participated in study 
STP-2279-002.
Adverse Events and Serious Adverse Events – AEs will be categorized using Medical 
Dictionary for Regulatory Activities (MedDRA) Version 22.1 or later.  Summaries will be 
presented for all treatment-emergent AEs, AEs determined by the Investigator to be treatment-
related, serious adverse events (SAEs), AEs causing withdrawal from study, AEs causing 
discontinuation of Revcovi, and non-serious AEs. The intensity of toxicities will be graded by 
the Investigator as mild, moderate, or severe as described in Section 12.2.5. In addition to being 
summarized as AEs, infectious complications and hospitalizations are considered efficacy 
measures as described in Section 10.8.  
AE incidence will be calculated based on the number of subjects per AE category. For each 
subject who has multiple AEs classified to the same category, that subject will be tabulated 
under the maximum toxicity intensity for that AE category. The incidence of AEs will be 
tabulated by MedDRA system organ class and preferred term.
An AE onset between the date of the first dose of Revcovi and 30 days after the last dose of 
Revcovi is considered as a treatment-emergent AE. 
Laboratory Safety Data – Hematology, chemistry, and urinalysis data will be summarized by 
timepoint of collection and by treatment group.  In addition, listings for laboratory data will be 
presented identifying clinically significant abnormal results and out-of-normal range values 
will be listed. 
Other Safety Data – The results of antibodies against Revcovi and antibodies against PEG will 
be summarized. The relationships between immunogenicity, biochemical endpoints, and the 
clinical toxicities will be examined as appropriate.  Concomitant medications and findings in 
physical examinations will be listed and described textually as recorded in the CRF.  
Descriptive statistics of vital signs measurements as well as changes from baseline will be 
tabulated; abnormal vital sign values will be reported and summarized as AEs. 
13.2.3.6
Clinical Status Analysis 
Analyses of the following clinical status endpoints will be primarily descriptive, with data 
listings, graphical presentations, frequency tabulations, and summary statistics as appropriate. 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 69 of 85
Date: 04th February 2022

Infections: The number of clinically documented and microbiologically documented 
events

Incidence and duration (length of stay) of hospitalizations 

Growth: Height-for-age and weight-for-age Z-scores (for subjects > 18 years of age)

Overall survival 
13.2.3.7
Quality of Life Analysis 
Quality of life will be assessed for subjects up to 18 years old using the age-specific Pediatric 
Quality of Life Inventory (PedsQL).  Subjects over 18 years old will be assessed using the 
SF-36 and Primary Antibody Deficiency Quality of Life Questionnaire (PADQOL).   
For PedsQL, the four scales (Physical Functioning, Emotional Functioning, Social 
Functioning, School Functioning) and 3 summary scores (Psychosocial Health, Physical health 
and Total Scale) will be calculated and presented with summary statistics at each time point. 
Data will be summarized by age and stratified by previous participation in study STP-2279-
002.  
Subjects that age out of PedsQL into PADQOL will be summarized only in the PedsQL while 
their PADQOL will be listed.
13.2.4
Handling Missing, Repeated, Unused and Spurious Data 
The handling of missing, repeated, unused and spurious data will be described in the statistical 
analysis plan for the study. 
13.2.5
Reporting of Deviations to Statistical Methodology 
The methods for documenting deviations to the statistical methodology will be described in 
the statistical analysis plan for the study.  These deviations will be described in the clinical 
study report.
13.3 Interim Analyses
An interim analysis will be performed approximately 2 years after the first subject is enrolled.
13.4 Statistical Criteria for Termination of the Study
There are no statistical criteria for the termination of the study.

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 70 of 85
Date: 04th February 2022
14
ADMINISTRATIVE
14.1 Changes to Study Protocol
14.1.1
Protocol Amendments
Protocol changes must be in the form of a written amendment approved by Chiesi.  
Protocol amendments and necessary revisions to the informed consent form must be submitted 
by the Investigator to the local IRB/IEC and such amendments are implemented after written 
approval of the requisite IRB/IEC.  Protocol changes to eliminate an immediate hazard to a 
study subject may, at the direction of Chiesi, be implemented immediately by the Investigator.  
The Investigator must then immediately inform the IRB/IEC and obtain required approvals.  
If a protocol amendment requires revision to the informed consent form, the revised IRB/IEC 
approved form must be used to re-consent subjects currently enrolled in the study and the new 
form must be used to obtain consent from new patients prior to enrollment.
All amendments are submitted to local regulatory authorities by Chiesi as required by local 
regulation.
14.1.2
Protocol Deviations 
It is recommended that the Investigator and study staff adhere to the Suggested Schedule of 
Assessments and guidelines for therapeutic monitoring as described in the Revcovi PI.  
Deviations from the Suggested Schedule of Assessments and the Revcovi PI should be 
documented but do not need to be reported as protocol deviations, due to the nature of this 
registry study. 
Departures from the protocol involving informed consent, eligibility criteria, and Revcovi 
administration are reported to the reviewing IRB/IEC by the Investigator in accordance with 
the IRB’s/IEC’s requirements.
14.2 Study Termination
Chiesi reserves the right to temporarily or permanently discontinue the study at any site and at 
any time.  Reasons for study discontinuation may include, but are not limited to, the following:

Investigator non-compliance with the protocol, GCP guidelines or regulatory 
requirements 

Safety concerns

Discontinuation of the study protocol and/or all studies with Revcovi

Request to discontinue the study by a regulatory or health authority
Chiesi will promptly inform all Investigators and the requisite regulatory authorities if the 
study is suspended or terminated for safety reasons.  In the case of such suspension or 
termination, Chiesi will provide the Investigator with instructions regarding the disposition of 
subjects (e.g., termination of treatment, subject follow-up) currently on the study.  The 
Investigator promptly notifies the IRB/IEC and implement subject disposition instructions.  

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 71 of 85
Date: 04th February 2022
Should the study be terminated prematurely, unused study material may be returned to the 
Sponsor or designee
14.3 Ethics Compliance Statement
This study is conducted in accordance with the principles of the Declaration of Helsinki, the 
International Conference on Harmonisation Guidance on GCP and the requirements of federal 
regulatory authorities regarding the conduct of clinical trials and the protection of human 
subjects.  
14.3.1
Institutional Review Board/Ethics Committee 
The Investigator submits the protocol and subsequent amendments, the informed consent and 
any other material used to inform patients about the study to the local IRB/IEC for approval 
prior to enrolling any patient into the study.  The IRB/IEC should be duly constituted according 
to applicable regulatory requirements.  Approval must be in the form of a letter signed by the 
Chairperson of the IRB/IEC or the Chairperson’s designee, must be on IRB/IEC stationery and 
must include the protocol by name and/or designated number.  IRB/IEC approval of the 
informed consent form must be clearly indicated in the IRB/IEC approval letter (indicating 
version/date of the version approved) or by other means utilized by the IRB/IEC (e.g., IRB 
approval stamp on the approved version of the form).  If an Investigator is a member of the 
IRB/IEC, the approval letter must stipulate that the Investigator did not participate in the final 
vote, although the Investigator may participate in the discussion of the study.  
The Investigator also reports the progress of the study to the IRB/IEC on an annual basis or 
more frequently as required by the IRB/IEC.  The Investigator also promptly informs the 
IRB/IEC of:

SAEs that the Sponsor reports to regulatory authorities in an expedited manner, 

All changes in research activity

Protocol deviations, as required by Chiesi or the IRB/IEC

Other reports as required by the IRB/IEC

The completion, termination, or discontinuation of the study, and 

A final summary of the final results at the conclusion of the study as required by 
the IRB/IEC
Copies of all correspondence between the Investigator and the IRB/IEC is provided to Chiesi.
14.3.2
Informed Consent
The Investigator obtains written informed consent from each patient or the patient’s legal 
representative using the current IRB/IEC-approved version of the informed consent form prior 
to performing any study-related procedures.  The consent form used to document informed 
consent from study participants must contain the elements of informed consent as described in 
21 CFR, Part 50/ICH E6 Section 4.8.10, as applicable to this registry study..  

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 72 of 85
Date: 04th February 2022
The study records (i.e., patient source documents and applicable study logs) documents that 
informed consent was obtained prior to patient’s participation in the study. 
14.3.3
Health Insurance Portability and Accountability Act for studies 
conducted in the US
The Investigator must obtain authorization from the patient to use and/or disclose protected 
heath information (PHI) in compliance with the HIPAA of 1996.  
HIPAA authorization may be obtained as part of the informed consent form or in a separate 
document and includes:

Identification of the parties that can use and disclose PHI

Identification of the parties to whom PHI may be disclosed

A description of the PHI

A description of the purpose for use and disclosure

Information pertaining to the patient’s rights related to authorization

Information about the expiration of the authorization and how to revoke 
authorization

A statement about what may happen if authorization is not provided

A statement that once information has been disclosed, it may be disclosed again 
without further authorization.
For studies conducted outside the US, compliance with applicable local regulations must be 
followed. 
14.3.4
Confidentiality of Subject Records
It is the responsibility of the Investigator to ensure that the confidentiality of all subjects 
participating in the study and all of their medical information is maintained.  eCRFs and other 
documents submitted to Chiesi must not contain the name of a study participant.  Each subject 
in the study is identified by a unique identifier that is used within the eCRF and any other 
material submitted to Chiesi.  Any identifying information must be kept in a secure location 
with access limited to the study staff directly participating in the study. 
Personal medical information may be reviewed by representatives of Chiesi/designee, of the 
IRB or of regulatory authorities in the course of monitoring the progress of the study.  Every 
reasonable effort should be made to maintain such information as confidential.
The results of the study may be presented in reports, published in scientific journals or 
presented at medical meetings; however, subject names are never to be used in any reports 
about the study.

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 73 of 85
Date: 04th February 2022
14.4  Conflict of Interest 
The Investigator shall acknowledge, by signing the Investigator’s Statement/ Signature Page 
(Section 15) that the participation in this clinical study by the Investigator and his/her Sub-
Investigators discloses any conflicts of interest or confirms no conflicts of interest with the 
study.
14.4.1
Monitoring and Audits
During the course of the study, a clinical monitor assigned by Chiesi or their designee makes 
regularly scheduled visits to the investigational site to review the progress of the study.  The 
frequency of monitoring visits will depend on the enrollment rate and performance at each site.  
During each visit, the monitor reviews various aspects of the study including, but not limited 
to:

Compliance with the protocol

Compliance with the principles of GCP and regulatory requirements

Review of written informed consent forms for subjects enrolled 

Comparison of source documentation to data recorded on CRFs to assure the 
completeness and accuracy of data collected

Continued acceptability of facilities and staff

Review of essential documentation for the study
During scheduled monitoring visits, the Investigator and the investigational site staff must be 
available to meet with the study monitor in order to discuss the progress of the study, make 
necessary corrections to eCRF entries, respond to data clarification requests, and respond to 
any other study-related inquiries of the monitor.
In addition to the above, representatives of Chiesi’s auditing staff or government inspectors 
may review the conduct/results of the study at the investigational site.  The Investigator must 
promptly notify Chiesi of any audit requests by regulatory authorities.  The Investigator 
cooperates with the auditor(s), makes available to the auditor all requested documentation, and 
ensures that issues detected during the course of these audits are satisfactorily resolved.   The 
Investigator supplies Chiesi with copies of all documentation and correspondence related to 
regulatory agency audits as outlined in the Clinical Study Agreement between Chiesi/designee 
and the Investigator and/or Institution.  If the results of the audit result in a Form FDA-483 (or 
similar document from another regulatory agency), the Investigator promptly provides a copy 
to Chiesi and provides a copy of the draft response to Chiesi prior to submission to the 
regulatory agency.
14.5 Investigator Obligations
The Investigator is responsible to meet the obligations of clinical investigators as described in 
ICH GCP guidelines, the Declaration of Helsinki and U.S. federal regulations as defined in 
21 CFR Parts 50, 54, 56, and 312.  

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 74 of 85
Date: 04th February 2022
These obligations include, but are not limited to:
1. Protect the rights, safety and welfare of subjects under the Investigator’s care
2. Conduct the study in accordance with the approved study protocol 
3. Conduct the study in accordance with GCP guidelines and applicable federal, state and 
local regulations and laws
4. Ensure that the staff involved with the conduct of the study is knowledgeable on the study 
agents used, the study protocol, study procedures, and reporting requirements 
5. Properly obtain informed consent and HIPAA authorization from all subjects enrolled 
using the current IRB-approved forms
6. Prepare and maintain accurate and complete case histories for all subjects participating in 
this trial that document all study procedures performed and record all data required for this 
study protocol
7. Report all SAEs to the Sponsor and IRB/IEC (as necessary) within the timeframes 
described in this protocol
8. Report any changes in research activity and unanticipated problems involving risk to study 
participants promptly to the IRB/IEC.
9. Report all protocol deviations promptly to Chiesi/designee.  Significant deviations require 
prompt notification to the IRB/IEC.
10.  Provide the IRB/IEC with copies of reports of SAEs submitted by Chiesi to regulatory 
authorities in an expedited manner (e.g., Investigational New Drug [IND] Safety Reports) 
11. Provide Chiesi with complete and accurate financial information to allow submission of 
complete and accurate certification and disclosure statements to FDA as required.
The Investigator, or a licensed physician Sub-Investigator to which the Investigator has 
delegated responsibility, is required to administer or oversee the care of study subjects and 
review study data (e.g., AEs, laboratory data, treatment response data) in a timely manner.
14.6 Financial Disclosure
All Investigators and Sub-Investigators listed on any Form FDA 1572 supplied by the 
Investigator disclose the following information as required by 21 CFR, Part 54:
1. Any financial arrangement entered into between Chiesi/designee and the Investigator/Sub-
Investigator whereby the value of the compensation to the Investigator/Sub-Investigator 
for conducting the study could be influenced by the outcome of the study.
2. Any significant payments totaling more than $25,000 USD, exclusive of the costs of 
conducting this or other clinical studies, from Chiesi, such as a grant to fund ongoing 
research, compensation in the form of equipment, retainer for ongoing consultation, or 
honoraria.
3. Any proprietary interest in the test product.
4. Any significant equity interest in Chiesi in excess of $50,000 USD.

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 75 of 85
Date: 04th February 2022
The Investigator/Sub-Investigator shall promptly update financial disclosure information if 
any changes occur during the course of the study and for 1 year following completion of this 
study.  This financial disclosure requirement includes the spouse and the dependent children 
of the Investigator/Sub-Investigator. 
14.7 Quality Control and Quality Assurance of Study Data
14.7.1
Data Processing and Data Quality Assurance
All site-generated study data are entered into an eCRF via an EDC system. Site personnel 
enters data from assessments performed as part of the standard of care for their patients who 
are taking Revcovi. These assessments include height and weight measurements, vital signs, 
and safety and specialty laboratory test results. The data are entered into specific time periods 
(e.g., Baseline, month 3, month 6, etc) that are defined relative to the Revcovi start date. 
Patients are also assessed throughout the duration of the registry for any concomitant 
medications, hospitalizations, procedures, and AEs, and that information is also entered into 
the EDC system. There are automatic system queries based on programmed edit checks, and 
there are manual queries that result from review of the data by the data manager, CRA, or other 
project team members. System queries include future dates, out of window dates, and out of 
range vital signs. Manual queries include cross-form checks, duplicate dates, and discrepant 
information.
14.8 Study Records
The Investigator is responsible for preparing and maintaining adequate records to enable the 
conduct of the study to be documented.  Study records include, but are not limited to, regulatory 
documentation (Section 14.8.1) and subject records (Sections 14.8.2 and 14.8.3).
14.8.1
Regulatory Documentation
Prior to initiating the study, the Investigator provides the CRO or Chiesi the following 
documents:

A signed Form FDA 1572 or equivalent

A current curriculum vitae for the Investigator and each sub-Investigator 
listed on the Form FDA 1572

Copy of the current medical licenses for the Investigator and Sub-
Investigators, as applicable

Written IRB/IEC approval of the protocol, informed consent form and any other 
material provided to potential study participants with information about the study 
(e.g., advertisements)

A copy of the IRB/IEC-approved informed consent document and HIPAA/privacy 
authorization

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 76 of 85
Date: 04th February 2022

Current IRB/IEC membership list for the reviewing IRB/IEC and/or multiple 
project assurance number or an IRB organization number under the Federal Wide 
Assurance program

A signed Investigator Protocol Agreement (Section 15 of study protocol)

Completed financial disclosure form for the Investigator and all Sub-Investigators

Local reference laboratory documentation, including current laboratory 
certification, current laboratory normal values, and director’s CV
During the course of the study, the Investigator maintains current records to document 
regulatory compliance with the study including: the study protocol and amendments, all 
versions of the PI in effect during study conduct, signed Investigator Agreement protocol 
page(s),  Form FDA 1572 or equivalent , curricula vitae of the Investigator and sub-
Investigators, medical licenses of the Investigator and sub-Investigators, financial disclosure 
of the Investigator and sub-Investigators, IRB/IEC approvals of the protocol, protocol 
amendment(s), informed consent form(s), IRB/IEC membership list, IRB/IEC approved 
informed consent form(s), IRB/IEC correspondence, protocol deviations, study logs (as 
provided by Chiesi), drug dispensing and accountability records, safety reports, and all 
correspondence pertaining to the conduct of the study.  Regulatory documentation is reviewed 
by  Chiesi during monitoring visits to assure regulatory compliance. 
14.8.2
Source Documents
The Investigator maintains records in the form of clinical charts, medical records, original 
laboratory, radiology and pathology reports, pharmacy records, subject diary cards, etc.  The 
Investigator documents in the clinic chart or medical record the name and number of the study 
and the date on which the patient signed informed consent prior to the patient’s participation 
in the study.  Source documents must completely reflect the nature and extent of the subject’s 
medical care and must be available, with direct access, for verification against CRF entries 
when Chiesi or its representatives visit the investigational site.  All information obtained from 
source documents is to be kept in strict confidence.
14.8.3
Case Report Forms
All site-generated study data is entered into an electronic Case Report Form (eCRF) via an 
electronic data capture (EDC) system.  The eCRFs are not used as the primary method for 
collection of study data and eCRF entries must be supported by source documents maintained 
by the Investigator.  Only those site staff so authorized at the initiation of the study may enter 
data into an EDC system.  
The Investigator is responsible for the completeness and accuracy of all eCRF data as certified 
by the Investigator’s dated electronic signature within the EDC at the completion of the study.

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 77 of 85
Date: 04th February 2022
14.8.4
Access to Study Records
The Investigator makes available, via direct access, all records pertaining to the conduct of this 
study to Chiesi and its representatives, and auditors from domestic and foreign regulatory 
authorities to facilitate monitoring visits and study audits.
14.8.5
Records Retention
The Investigator retains the records of the study for 15 years, or for 2 years following the 
closure of the study.  Chiesi will notify Investigators when retention of study records is no 
longer required.  All study records must be maintained in a safe and secure location that allows 
for timely retrieval, if needed.
Study records that must be retained include storage media containing eCRF data, signed 
informed consents, regulatory documentation, source documents, clinic charts, medical 
records, laboratory results, radiographic reports, and other study-specific documentation.
Should the Investigator relocate or retire or should there be any changes in the archival 
arrangements for the study records, Chiesi must be notified.  The responsibility for maintaining 
the study records may be transferred to another suitable individual, but Chiesi must be notified 
of the identity of the individual assuming responsibility for maintaining the study records and 
the location of their storage.  If no other individual at the investigational site is willing to 
assume this responsibility, Chiesi assumes responsibility for maintaining the study records.
14.9 Publication Policy
Publication of study data is addressed in the Clinical Study Agreement between Chiesi and 
Investigator(s) and/or Institution(s).  
14.10 Financing and Insurance
Financing and Insurance are addressed in the Clinical Study Agreement between 
Chiesi/designee and the Investigator and/or Institution.  

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 78 of 85
Date: 04th February 2022
15
INVESTIGATOR AGREEMENT 
I have reviewed Chiesi Farmaceutici’s Protocol CLI-06814AA1-01 entitled “Single Arm, Open-Label, 
Multicenter, Registry Study of Revcovi (Polyethylene Glycol Recombinant Adenosine Deaminase [PEG-rADA]) 
Treatment in ADA-SCID Subjects Requiring Enzyme Replacement Therapy” and agree that it contains all the 
information necessary to conduct the study as required.  I will conduct the trial in accordance with the principles 
of ICH Good Clinical Practice and the Declaration of Helsinki.  
I will maintain as confidential all written and verbal information provided to me by Chiesi, including but not 
limited to, the protocol, case report forms, material supplied at investigator meetings, minutes of teleconferences, 
etc.  Such material will only be provided as necessary to site personnel involved in the conduct of the trial, the 
IRB or IEC, or local regulatory authorities.   
I will obtain written informed consent from each prospective trial subject or each prospective trial subject’s legal 
representative prior to conducting any protocol-specified procedures.  The consent form used will have the 
approval of the local IRB or IEC.
I will maintain adequate source documents and record all observations, treatments, and procedures pertinent to 
registry subjects in their medical records.  I will accurately complete the electronic case report forms in a timely 
manner.  I will ensure that my facilities and records are available for inspection by representatives of Chiesi, the 
local IRB or IEC or local regulatory authorities.  I will ensure that my staff and I are available to meet with 
representatives of Chiesi during regularly scheduled monitoring visits.
My signature below indicates that my participation in this clinical study affirms the disclosure of any conflicts of 
interest for me or my sub-investigators with the study.
Investigator’s Name (Print)
Investigator’s Signature
Date

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 79 of 85
Date: 04th February 2022
16
REFERENCES
1.
Aiuti A, Slavin S, Aker M, et al. Correction of ADA-SCID by stem cell gene therapy combined 
with nonmyeloablative conditioning. Science. 2002;296(5577):2410-2413.
2.
Aiuti A, Cassani B, Andolfi G, et al. Multilineage hematopoietic reconstitution without clonal 
selection in ADA-SCID subjects treated with stem cell gene therapy. J Clin Invest. 
2007;117(8):2233-2240.
3.
Aiuti A, Cattaneo F, Galimberti S, et al. Gene therapy for immunodeficiency due to adenosine 
deaminase deficiency. N Engl J Med. 2009;360(5):447-458.
4.
Arredondo-Vega FX, Santisteban I, Daniels S, Toutain S, Hershfield MS. Adenosine deaminase 
deficiency: genotype-phenotype correlations based on expressed activity of 29 mutant alleles. Am 
J Hum Genet. 1998;63(4):1049-1059.
5.
Booth C, Hershfield M, Notarangelo L, et al. Management options for adenosine deaminase 
deficiency; proceedings of the EBMT satellite workshop (Hamburg, March 2006). Clin Immunol. 
2007;123(2):139-147.
6.
Booth C, Gaspar HB. Pegademase bovine (PEG-ADA) for the treatment of infants and children 
with severe combined immunodeficiency (SCID). Biologics. 2009;3:349-358.
7.
Candotti F, Shaw KL, Muul L, et al. Gene therapy for adenosine deaminase-deficient severe 
combined immune deficiency: clinical comparison of retroviral vectors and treatment plans. Blood. 
2012;120(18):3635-3646.
8.
Cappelli B, Aiuti A. Gene therapy for adenosine deaminase deficiency. Immunol Allergy Clin North 
Am. 2010;30(2):249-260.
9.
Cavazzana-Calvo M, Lagresle C, Hacein-Bey-Abina S, Fischer A. Gene therapy for severe 
combined immunodeficiency. Annu Rev Med. 2005;56:585-602.
10.
Engel BC, Kohn DB, Podsakoff GM. Update on gene therapy of inherited immune deficiencies. 
Curr Opin Mol Ther. 2003;5(5):503-507.
11.
Engel BC, Podsakoff GM, Ireland JL, et al. Prolonged pancytopenia in a gene therapy subject with 
ADA-deficient SCID and trisomy 8 mosaicism: a case report. Blood. 2007;109(2):503-506.
12.
Farinelli G, Capo V, Scaramuzza S, Aiuti A. Lentiviral vectors for the treatment of primary 
immunodeficiencies. J Inherit Metab Dis. 2014;37(4):525-533.
13.
Gaspar HB, Thrasher AJ. Gene therapy for severe combined immunodeficiencies. Expert Opin Biol 
Ther. 2005;5(9):1175-1182.
14.
Gaspar HB, Bjorkegren E, Parsley K, et al. Successful reconstitution of immunity in ADA-SCID 
by stem cell gene therapy following cessation of PEG-ADA and use of mild preconditioning. Mol 
Ther. 2006;14(4):505-513.
15.
Gaspar HB, Aiuti A, Porta F, Candotti F, Hershfield MS, Notarangelo LD. How I treat ADA 
deficiency. Blood. 2009;114(17):3524-3532.
16.
Gaspar HB, Qasim W, Davies EG, Rao K, Amrolia PJ, Veys P. How I treat severe combined 
immunodeficiency. Blood. 2013;122(23):3749-3758.
17.
Qasim W, Gaspar HB, Thrasher AJ. Gene therapy for severe combined immune deficiency. Expert 
Rev Mol Med. 2004;6(13):1-15.
18.
Taupin P. Drug evaluation: ADA-transduced hematopoietic stem cell therapy for ADA-SCID. 
IDrugs. 2006;9(6):423-430.

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 80 of 85
Date: 04th February 2022
Appendix 1:
Suggested Schedule of Assessments for Adagen-Transitioning Subjects
Enrollmen
t
TW = Treatment Week
TM = Treatment Month
Procedure
ENR
TW 
4
±1 wk)
TW 
8
(±1 wk)
TW 
12
(±1 wk)
TM 
6
(±3 wk)
TM 
9
(±3 wk)
TM 
12
(±3 wk)
TM 
15
(±3 wk)
TM 
18
(±3 wk)
M 
21
(±3 wk)
TM 24/ DC
(±3 wk)
Informed assent/consent
X
Demographics
X
Medical history (including ADA-
Mutation results if available)
X
Inclusion/exclusion criteria 
X
Physical examination (including 
height and weight)
X
X
X
X
X
X
X
X
X
X
X
Vital signs 
X
X
X
X
X
X
X
X
X
X
X
Concomitant medications 
X
X
X
X
X
X
X
X
X
X
X
Safety Laboratory Assessments 
(if available)
X
X
X
X
X
X
X
X
X
X
X
Total trough erythrocyte dAXP
X
X
X
X
Trough Plasma ADA activity1
X
X
X
X
X
X
X
X
X
X
X
B-/T-/NK-lymphocyte subset
X
X
X
X
X
X
X
X
X
Quantitative immunoglobulins
X
X
X
X
X
Immunogenicity2
X
X
X
X
X
X
X
X
X
X
X
Quality of Life
X
X3
X
X3
X
X
X
Adverse events
X
X
X
X
X
X
X
X
X
X
Potential ADA inhibitors and Ig 
replacement therapy
X
X
X
X
X
X
X
X
X
X
X
Revcovi Dosing and Compliance
X
X
X
X
X
X
X
X
X
X
X
1 If a decline in ADA activity levels persists, immune function and clinical status will be monitored more closely, and precautions will be taken to minimize the risk of infection. 
Evaluation of immune function includes B-/T-/NK-lymphocyte subsets, quantitative immunoglobulins, and adequate immune reconstitution in accordance with the Revcovi 
Package insert and per Investigator discretion.
2 Immunogenicity should be assessed in accordance with the Revcovi Package Insert.
Survival will be monitored throughout the study; for subjects undergoing gene therapy or stem cell transplant, survival will be assessed at 1 month and 6 months post final dose.  
3 The Pediatric Quality of Life Inventory (PedsQL) will be performed for infants aged 1 to 12 months only.  All subjects up to age 18 years will be assessed at all other indicated 
visits using the age specific PedsQL.  Subjects over 18 years will be assessed using the SF36 and Primary Antibody Deficiency Quality of Life Questionnaire (PADQOL). 
Quality of life assessment data will be collected prospectively for 24 months after starting Revcovi from study participants via scripted phone calls by the study call center and 
QoL responses will be entered directly into the EDC system. Note - The listing for the schedule of assessments provides a template for reporting of monitoring and is not a rigid 

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 81 of 85
Date: 04th February 2022
requirement. Clinicians should individualize the schedule of monitoring to assess the effect of Revcovi on trough plasma activity of ADA, erythrocyte dAXP, and immune 
function (lymphocyte counts, lymphocyte subsets and immune response) while balancing the risk of phlebotomy and subject visit burden.  

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 82 of 85
Date: 04th February 2022
Appendix 1: Suggested Schedule of Assessments for Adagen-Transitioning Subjects (cont.)
TM = Treatment Month
HSCT or HSC-GT
Procedure
TM 27
(±3 wk)
TM 30
(±3 wk)
TM 33
(±3 wk)
TM 36
(±3 wk)
TM 39
(±3 wk)
TM 42
(±3 wk)
TM 45
(±3 wk)
TM 48/ DC
(±3 wk)
Month 1
Month 6
Informed assent/consent
Demographics
Medical history (including ADA- 
Mutation results if available)
Inclusion/exclusion criteria
Physical examination (including 
height and weight)
X
X
X
X
X
X
X
X
Vital signs
X
X
X
X
X
X
X
X
Concomitant medications
X
X
X
X
X
X
X
X
Safety Laboratory Assessments 
(if available)
X
X
X
X
X
X
X
X
X
X
Total trough erythrocyte dAXP
           X
        X
X
X
Trough Plasma ADA activity1
X
X
X
X
X
X
X
X
B-/T-/NK-lymphocyte subset
X
X
X
X
X
X
X
X
Quantitative immunoglobulins
X
X
X
X
Immunogenicity2
X
X
X
X
X
X
X
X
Quality of Life
Adverse events
X
X
X
X
X
X
X
X
X
X
Potential ADA inhibitors and Ig
replacement therapy
X
X
X
X
X
X
X
X
Revcovi Dosing and Compliance
X
X
X
X
X
X
X
X
Subjects undergoing HSCT or HSC-GT will be followed one month and again at six months after final Revcovi dose to assess for 
AEs and survival.

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 83 of 85
Date: 04th February 2022
Appendix 2:
Suggested Schedule of Assessment for Adagen-Naïve Subjects
Enrollment
TW = Treatment Week
Procedure
ENR
TW 2
(±3 d)
TW 4 
(±3 d)
TW 6
(±3 d)
TW 8
(±3 d)
TW 10
(±3 d)
TW 12
(±3 d)
Informed Assent / Consent
X
 
 
 
 
 
 
Demographics
X
 
 
 
 
 
 
Medical History
X
 
 
 
 
 
 
Inclusion / Exclusion Criteria
X
 
 
 
 
 
 
Physical Examination (including height and 
weight)
X
 X
X
X
X
 X
X
Vital Signs 
X
 X
X
X
X
 X
X
Concomitant medications 
X
 X
X
X
X
 X
X
Safety Laboratory Assessments (if available)
X
 X
X
X
X
 X
X
Total Trough Erythrocyte dAXP
X
X
X
X
X
X
X
Trough Plasma ADA activity1
X
X
X
X
X
X
X
B-/T-/NK-lymphocyte subset
X
 
X
 
X
 
X
Quantitative immunoglobulins
X
 
X
 
X
 
X
ADA-Mutation analysis (if available)
X
 
 
 
 
 
 
Immunogenicity2
X
X
X
X
X
X
X
Quality of Life
X
X3
Adverse events
X
X
X
X
X
X
Potential ADA inhibitors and Ig replacement 
therapy
X
X
X
X
X
X
X
Revcovi Dosing and Compliance
X
X
X
X
X
X
X

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 84 of 85
Date: 04th February 2022
Appendix 2:
Suggested Schedule of Assessment for Adagen-Naïve Subjects (continued)
TM = Treatment Month
Procedure
TM 4
(±1 wk)
TM 5
(±1 wk)
TM 6
(±1 wk)
TM 7
(±1 wk)
TM 8
(±1 
wk) 
TM 9
(±1 wk)
TM 12
(±3 wk)
TM 15
(±3 wk)
TM 18
(±3 wk)
TM 
21
(±3 
wk)
TM 24 /DC
(±3 wk)
Physical Examination 
(including height and weight)
X
X
X
X
X
X
X
X
X
X
X
Vital Signs 
X
X
X
X
X
X
X
X
X
X
X
Concomitant medications 
X
X
X
X
X
X
X
X
X
X
X
Safety Laboratory Assessment 
(if available)
X
X
X
X
X
X
X
X
X
Total Trough Erythrocyte 
dAXP
X
X
X
X
Trough Plasma ADA activity1 
X
X
X
X
X
X
X
B-/T-/NK-lymphocyte subset
X
X
X
X
X
X
X
X
X
X
X
Quantitative immunoglobulins
X
X
X
X
Immunogenicity2
X
X
X
X
X
X
X
X
X
Quality of Life
X
X3
X
X
X
Adverse events
X
X
X
X
X
X
X
X
X
X
X
Potential ADA inhibitors and 
Ig replacement therapy
X
X
X
X
X
X
X
X
X
X
X
Revcovi Dosing and 
Compliance
X
X
X
X
X
X
X
X
X
X
X
1 If a decline in ADA activity levels persists, immune function and clinical status should be monitored more closely, and precaution will be taken to minimize the risk of 
infection. Evaluation of immune function includes B-/T-/NK-lymphocyte subsets, quantitative immunoglobulins, and adequate immune reconstitution in accordance with the 
Revcovi Package insert and per Investigator discretion.
2 Immunogenicity should be assessed in accordance with the Revcovi Package Insert.
Survival will be monitored for the duration of the study; for subjects undergoing gene therapy or stem cell transplant, survival will be assessed at 1 month and 6 months post 
final dose.

Protocol CLI-06814AA1-01
CONFIDENTIAL
Version 5.0
Page 85 of 85
Date: 04th February 2022
3 The Pediatric Quality of Life Inventory (PedsQL) will be performed for infants aged 1 to 24 months and for toddlers aged 2 to 4 years only using the age-specific inventory.  
All subjects up to age 18 years will be assessed at all other indicated visits using the age-specific PedsQL.  Subjects over 18 years will be assessed using the SF-36 and Primary 
Antibody Deficiency Quality of Life Questionnaire (PADQOL). Quality of life assessment data will be collected prospectively for 24 months after starting Revcovi from study 
participants via scripted phone calls by the study call center and QoL responses will be entered directly into the EDC system. 
Note - The listing for the schedule of assessments provides a template for reporting of monitoring and is not a rigid requirement. .Clinicians should individualize the schedule 
of monitoring to assess the effect of Revcovi on trough plasma activity of ADA, erythrocyte dAXP, and immune function (lymphocyte counts, lymphocyte subsets and immune 
response) while  balancing the risk of phlebotomy and subject visit burden.
Appendix 2:
Suggested Schedule of Assessment for Adagen-Naïve Subjects (continued)
TM = Treatment Month
HSCT or HSC-GT
Procedure
TM 27
(±3 wk)
TM 30
(±3 wk)
TM 33
(±3 wk)
TM 36
(±3 wk)
TM 39
(±3 wk)
TM 42
(±3 wk)
TM 45
(±3 wk)
TM 48/ DC
(±3 wk)
Month 1
Month 6
Informed assent/consent
Demographics
Medical history (including ADA- 
Mutation results if available)
Inclusion/exclusion criteria
Physical examination (including 
height and weight)
X
X
X
X
X
X
X
X
Vital signs
X
X
X
X
X
X
X
X
Concomitant medications
X
X
X
X
X
X
X
X
Safety Laboratory Assessments 
(if available)
X
X
X
X
X
X
X
X
X
X
Total trough erythrocyte dAXP
           X
        X
X
X
Trough Plasma ADA activity1
X
X
X
X
X
X
X
X
B-/T-/NK-lymphocyte subset
X
X
X
X
X
X
X
X
Quantitative immunoglobulins
X
X
X
X
Immunogenicity2
X
X
X
X
X
X
X
X
Quality of Life
Adverse events
X
X
X
X
X
X
X
X
X
X
Potential ADA inhibitors and Ig
replacement therapy
X
X
X
X
X
X
X
X
Revcovi Dosing and Compliance
X
X
X
X
X
X
X
X