Clinical trial NCT01734850
Conditions: Human Immunodeficiency Virus
Keywords: HIV-1
Sponsor: Calimmune, Inc.
Start date: 2013-04-01; Completion date: 2017-11-01
Enrollment: 13 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is an early phase research study looking at whether an experimental gene transfer, LVsh5/C46 (also known as Cal-1), is safe and if it can protect the immune system from the effects of HIV without the use of antiretroviral drugs.

Cal-1 is an experimental gene transfer agent designed to inhibit HIV infection through 2 active parts:

1. Removing a protein named CCR5 from bone marrow and white blood cells
2. Producing a protein named C46 on bone marrow and white blood cells

Detailed description:
It is estimated that 33 million individuals are currently infected with HIV. HIV/AIDS is a disease that impairs immune function, primarily by decreasing CD4+ T lymphocytes. The progression can be contained by daily dosing with antiretroviral therapy (ART) but there are side effects that can be treatment limiting, and the development of HIV drug resistance can force the physician to modify the ART regimen. There are no effective vaccines currently available for HIV.

LVsh5/C46 (also known as Cal-1) is a dual therapeutic, self-inactivating lentiviral vector that encodes for both a short hairpin RNA against the HIV-1 co-receptor CCR5 (sh5) and a HIV-1 fusion inhibitor, C46 and inhibits two processes required for HIV-1 infection:

1. Binding of the virus to the cellular CCR5 co-receptor and
2. Fusion of the virus with the host cell

The rationale is that Cal-1 introduced into hematopoietic progenitor/stem cells (HSPC) and mature CD4+ T lymphocytes will protect these cells and their progeny cells from HIV-1 infection and its pathogenic sequelae. This may provide a continuous means of controlling HIV-1 after a single or infrequent dose(s), thereby decreasing or delaying (partially or completely) the need for antiretroviral drug therapy.

Arms: arm 1: Cal-1 modified HSPC and Cal-1 modified CD4+ T lymphocytes without busulfan preconditioning arm 2: Cal-1 modified HSPC and Cal-1 modified CD4+ T lymphocytes, with single 4mg/kg busulfan dose administered as pre-conditioning for transplant arm 3: Cal-1 modified HSPC and Cal-1 modified CD4+ T lymphocytes, with two 4mg/kg busulfan doses administered as pre-conditioning for transplant
Interventions: intervention 1: Busulfan intervention 2: Cal-1 modified HSPC intervention 3: Cal-1 modified CD4+ T lymphocytes
Intervention descriptions: intervention 1: Intravenous busulfan intervention 2: Hematopoietic progenitor/stem cells (HSPC) modified with LVsh5/C46 (Cal-1) intervention 3: CD4+ T lymphocytes modified with LVsh5/C46 (Cal-1)

Protocol documents:
Prot_000.pdf: 
 
 
 
AN ADAPTIVE PHASE I/II STUDY OF THE SAFETY OF CD4+ T 
LYMPHOCYTES AND CD34+ HEMATOPOIETIC STEM/PROGENITOR 
CELLS TRANSDUCED WITH LVsh5/C46, A DUAL ANTI-HIV GENE 
TRANSFER CONSTRUCT, WITH AND WITHOUT CONDITIONING WITH 
BUSULFAN IN HIV-1 INFECTED ADULTS PREVIOUSLY EXPOSED TO 
ART 
 
CLINICAL PROTOCOL CAL-USA-11 
 
 
 
Sponsor*: 
Calimmune, Inc. 
 
* Calimmune is a global organization that operates as Calimmune Australia Pty 
Ltd: Level 8, Lowy Packer Building 405 Liverpool Street, Darlinghurst NSW 2010, 
Sydney, Australia and Calimmune, Inc: 5151 E. Broadway Blvd., Suite 1020, 
Tucson, AZ 85711, USA. The term “Sponsor” is used throughout the protocol to 
represent both these legal entities, collectively known as Calimmune. 
 
Document version: 
8.0 
 
Document date:  
08 July 2015 
 
 
 
 
CONFIDENTIALITY STATEMENT 
This document is confidential and the property of Calimmune Australia Pty Ltd. Calimmune Australia Pty Ltd is a wholly-owned 
subsidiary of Calimmune, Inc. No part of this document may be transmitted, reproduced, published, or used without the prior 
written authorization of Calimmune, Inc. 
 


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CONTACT INFORMATION 
Function 
Contact 
Address 
Telephone / email 
Medical Monitoring 
   
Calimmune Inc. 
129 N. Hill Avenue 
Suite 105 
Pasadena, CA 91106 USA 
 
 
Project Director 
 
Calimmune Inc. 
$VDERYH 
 
Project Management 
 
Calimmune Inc. 
$VDERYH 
 
Monitoring 
 
 
Calimmune Inc. 
$VDERYH 
 
SAE & Pregnancy 
Reporting 
- 
 
 
 
Data Management 
 
 
  
$VDERYH 
 
 
 
eCRF helpdesk 
- 
 
 
 
Cell Manufacturing 
 
 
 
 
 
 
Quality Assurance  
, Calimmune Australia Pty Ltd 
Level 8, Lowy Packer Bldg. 
405 Liverpool Street, 
Darlinghurst NSW 2010 
Sydney, Australia 
 
Clinical Laboratories 
Routine analysis
 
 
 

 
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Busulfan PK
 
 
 
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Cal-1Marking & 
Expression analysis 
 
 
 
 
C46 Immunogenicity 
C46 antibody 
 
 
C46 cellular
 
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
Integration analysis
 
 
 
 
 
 
 
 
 
 
RCL 
 
 
 
 
 

Note: If the name, address or contact details of any of the above representatives changes during the course of the study, this 
section will be updated, without the requirement for a protocol amendment.  
 
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Version 8.0 
GLOSSARY OF ABBREVIATIONS 
AE 
Adverse event 
ALT (SGPT) 
Alanine aminotransferase 
ANC 
Absolute neutrophil count 
AST (SGOT) 
Aspartate aminotransferase 
ART 
Antiretroviral Therapy 
BD 
Twice daily 
BP 
Blood pressure 
Cal-1 
LVsh5/C46, a Dual Anti-HIV Gene Transfer Construct 
CRO 
Contract Research Organization 
CRF 
Case report form 
DNA 
Deoxyribonucleic acid 
DSMB 
Data Safety Monitoring Board 
FBC 
Full blood count 
FDA 
Food and Drug Administration 
GALT 
Gut-associated lymphoid tissue 
GCP 
Good clinical practice 
GGT 
Gamma-glutamyl transferase 
GMP 
Good manufacturing practice 
G-CSF 
Granulocyte colony-stimulating factor 
HIV-1 
Human immunodeficiency virus type 1 
HSPC 
CD34+ Hematopoietic stem/progenitor cells 
HSPCtn 
Cal-1 transduced CD34+ Hematopoietic stem/progenitor cells 
IB 
Investigator’s brochure 
ICH 
International Conference on Harmonization 
IND 
Investigational new drug 
LLN 
Lower limit of normal 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRC 
Medical Review Committee 
NSAID 
Non-steroidal anti-inflammatory drugs 
PBMC 
Peripheral blood mononuclear cells 
PICF 
Participant informed consent form 
QD 
Once daily 
SAE 
Serious adverse event 
SOP 
Standard operating procedure 
SUSAR 
Serious and Unexpected Suspected Adverse Reaction 
Ttn 
Cal-1 transduced CD4+ T lymphocytes 
ULN 
Upper limit of normal 
WBC 
White blood count 
 
 


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SYNOPSIS 
Title: An adaptive Phase I/II study of the safety of CD4+ T lymphocytes and CD34+ 
hematopoietic stem/progenitor cells transduced with LVsh5/C46, a dual anti-HIV gene transfer 
construct, with and without conditioning with busulfan in HIV-1 infected adults previously 
exposed to ART. 
BB-IND number: 

RAC number: 
Public Registration: ClinicalTrials.gov (NCT01734850) 
Sponsor: Calimmune, Inc. 
Indication: Adult individuals with HIV-1 infection, who have previously received ART, but are 
not currently on any antiretroviral medication. 
Participating country(s): USA 
Anticipated number of sites: 2 
Anticipated number of subjects: up to 12 
BACKGROUND 
LVsh5/C46 (hereafter referred to as Cal-1) is a dual therapeutic, self-inactivating lentiviral vector 
that inhibits two processes required for HIV-1 infection: 1) Binding of the virus to the cellular 
CCR5 co-receptor and 2) Fusion of the virus with the host cell. The vector encodes for both a short 
hairpin RNA against the HIV-1 co-receptor CCR5 (sh5) ($QHWDO and a HIV-1 fusion 
inhibitor, C46, ((JHOKRIHUHWDO). The two active anti-HIV-1 agents in the vector (sh5 and 
C46) have been shown individually to be effective in inhibiting HIV-1 replication and decreasing 
HIV-1 induced cytopathicity in HIV-1 challenge tissue culture experiments, and there are strong 
pre-clinical data in animal models that C46 is very efficient at inhibiting HIV-1 replication and its 
pathogenic effects ((JHOKRIHUHWDO=DKQHWDO<RXQDQHWDO).  Combined they 
are more effective at inhibiting HIV-1.  Once integrated into the target cell, sh5 driven by the H1 
promoter, produces a small interfering RNA (siRNA) that reduces the level of CCR5 on the cell 
surface. The expression of the C46 component, that is derived from the HIV-1 envelope 
glycoprotein gp41, is driven by the ubiquitin C promoter. C46 will act as a membrane-anchored C-
peptide that inhibits fusion of the HIV-1 envelope to the host cell membrane. In a Phase I clinical 
trial, C46 was shown to be safe with persistent detection of gene-marked CD4+ T lymphocytes in 
HIV+ subjects (YDQ/XQ]HQHWDO). 
CCR5 is the major co-receptor for HIV-1. Studies on a naturally occurring human mutation in the 
CCR5 gene, known as ‘delta-32 ('32) CCR5’ have shown that HIV-1 is unable to establish 
infection in homozygous individuals and disease progression is significantly slower in 
heterozygotes (,RDQQLGLVHWDO2¶%ULHQDQG1HOVRQ). This protective effect has been 
shown to be transferable: In 2007, an allogenic bone marrow transplant was performed using '32 
CCI


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mutant CCR5 hematopoietic stem/progenitor cells (HSPC) into a wild type CCR5 HIV-1 positive 
individual. The transplant was reported as ‘functionally curative for HIV’ (Hütter et al, 2009). 
The rationale for the proposed clinical trial is that Cal-1 introduced into HSPC and CD4+ T 
lymphocytes will protect these cells and their progeny cells from HIV-1 infection and its 
pathogenic sequelae. This protective effect is predicted to act to lower HIV-1 RNA and increase 
CD4+ T lymphocyte counts, thereby decreasing or delaying (partially or completely) the need for 
antiretroviral drug therapy. 
This is a phase I/II human clinical study of Cal-1. Prior clinical studies in the area of HIV-1 and 
gene therapy have pointed to the therapeutic potential of the genetic modification of HSPC and 
CD4+ T lymphocytes (Aiuti et al 2002; Kang et al 2002; Malech et al 2004; Barese et al 2004; 
Ott et al 2006; Rossi et al 2007; van Lunzen et al 2007; Mitsuyasu et al 2009; Gaspar et al 2009; 
Aiuti et al 2009; Cartier et al 2009; Boztug et al 2010; Cavazzana-Calvo et al 2010; Symonds et 
al 2010). 
OVERVIEW OF STUDY DESIGN 
This is an adaptive design study to evaluate the safety and feasibility of Cal-1 transduced HSPC 
and CD4+ T lymphocytes in HIV-1 infected subjects who have previously been exposed to ART 
but are not currently taking any antiretroviral agent. Three cohorts of at least 3 subjects each will 
be enrolled: 
Cohort 1: No busulfan conditioning 
Cohort 2: Conditioning with a single dose of 4mg/kg busulfan. 
Cohort 3: Conditioning with two doses of busulfan, with first dose of 4, 3 or 2 mg/kg and second 
dose based on real-time pharmacokinetic-guided dosing to reach targeted drug exposure 
(AUC). 
Progressive enrollment of Cohort 1, then Cohort 2 and then Cohort 3 is dependent on the 
recommendation of an independent Data Safety Monitoring Board (DSMB). 
The primary objective is to evaluate the safety and feasibility of using Cal-1 transduced HSPC 
(HSPCtn) and CD4+ T lymphocytes (Ttn), including the use of various doses of busulfan to increase 
HSPCtn engraftment. The trial will also assess the level of gene-marked cells and any impact on 
HIV-1 RNA and CD4+ T lymphocyte count, as well as other exploratory parameters. 
Subjects will have two sets of cell collection procedures (aphereses) performed; first a single 5L 
apheresis to collect unstimulated CD4+ T lymphocytes, followed by a second set of two, larger 
volume (15L) aphereses to collect CD34+ HSPC on days 4 and 5 of mobilization. The mononuclear 
cell populations obtained from each of these two collection procedures will be separated into 
purified CD4+ T lymphocytes and CD34+ HSPC, respectively and processed (transduced, cultured 
and cryopreserved) separately. 


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The primary endpoint for all subjects will be at 48 weeks post-infusion, after which they may 
continue follow-up for up to one additional year in the Follow-up Extension phase. All subjects 
will transfer to a separate long-term follow-up protocol that will monitor each subject for potential 
long term adverse effects of Cal-1. Secondary data points are collected up to study completion or 
until early withdrawal or secondary analysis endpoint criteria is met (discontinuation), whichever 
occurs first. Subjects should commence ART at any time during the study if CD4+ T lymphocyte 
counts are confirmed to decline < 350 cells/µl (mm3) or to less than 1/3 of the CD4+ T cell % at 
the Pre-busulfan Assessment visit, if plasma HIV RNA exceeds 250,000 copies/µl or > 20-fold 
increase from the Pre-busulfan Assessment visit, or in event of pregnancy (as defined in Section 
6.2.4).  
During the post-infusion study phase, periodic evaluations, as described in the Schedule of Events, 
are designed to assess safety and feasibility, as well as preliminary evidence of efficacy. 
OBJECTIVES 
PRIMARY OBJECTIVE 
To evaluate the safety and feasibility of the introduction of Cal-1 gene-transduced, hematopoietic 
cell populations (Ttn and HSPCtn) with or without intravenous busulfan conditioning at a range of 
doses in HIV-1-infected adults who have previously been on ART. 
SECONDARY OBJECTIVES 
To assess; 
1. The extent of HSPCtn contribution to hematopoiesis and Ttn survival by evaluation of Cal-1 
marking and expression in peripheral blood at time points up to study completion or 
discontinuation. 
2. The extent of HSPCtn contribution to hematopoiesis and Ttn survival by evaluation of Cal-1 
marking and expression in gut-associated lymphoid tissue (GALT). 
3. The potential benefit of busulfan conditioning as determined by; 
a. The extent of engraftment and differentiation of HSPCtn over time by evaluation of Cal-
1 marking and expression in peripheral blood subpopulations (monocytes, granulocytes, 
CD4+ and CD8+ lymphocytes)  
b. The extent of HSPCtn engraftment by evaluation of Cal-1 marking and expression in 
bone marrow at Week 12 
4. The potential efficacy of Cal-1 in controlling HIV-1 infection for each subject, as measured by; 
a. Plasma HIV-1 RNA relative to  the Pre-busulfan Assessment visit 
b. Plasma HIV-1 RNA over time 
c. CD4+ T lymphocyte count, percentage and CD4+/CD8+ T lymphocyte ratio relative to 
the Pre-busulfan Assessment visit 
d. CD4+ T lymphocyte count, percentage and CD4+/CD8+ T lymphocyte ratio over time 


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e. Time to commencement of antiretroviral therapy (as defined in Section 6.2.4) 
The endpoint for these secondary analyses is study completion, withdrawal, or until 
discontinuation due to secondary analysis endpoint criteria (as defined in Sections 8 and 9). 
5. Impact on lymphocyte development for each subject, as measured by changes in thymopoiesis 
and maturation markers in peripheral blood relative to pre-infusion baseline, and impact on 
chronic inflammation for each subject as measured by changes in inflammation markers in 
peripheral blood relative to pre-infusion baseline over time. 
6. A tropism shift from R5 to dual/mixed or X4 at any time point. 
STUDY POPULATION 
Up to 12 subjects will be enrolled; at least 3 subjects per cohort. The 3 cohorts are defined according 
to the dose of busulfan (Busulfex®) to be administered for pre-infusion reduced intensity 
conditioning. The doses of busulfan are chosen to have a non-myeloablative conditioning effect. 
Two different busulfan dose ranges are being assessed in order to identify the most effective dose 
that can safely facilitate engraftment and maximize the contribution of Cal-1 transduced CD34+ 
HSPCs to hematopoiesis. Each cohort will receive Cal-1 transduced HSPC and CD4+ T 
lymphocytes. 
The study is enrolling subjects who have previously been treated with antiretroviral therapy (ART), 
but are no longer receiving it. This target population will allow assessment of baseline 
characteristics of HIV-1 quantity, tropism and phenotype, as well as changes in HIV-1 RNA and 
CD4+ T lymphocyte counts without the requirement for a structured treatment interruption. In 
addition, each subject will serve as is/her own control for HIV-1 RNA and CD4+ T lymphocyte 
count comparisons pre- and post- cellular infusions. The screening eligibility criteria require that a 
subject be off ART for at least 6 weeks prior to screening. In terms of CD4+ T lymphocyte count, 
subjects must not have a documented historical CD4+ T lymphocyte count of < 250 cells/µl (mm3) 
and a minimum count at screening of ≥ 500 cells/µl (mm3). This is to provide safe limits for subjects 
who are anticipated to continue without ART, to enable evaluation of the effect of Cal-1 on HIV-
1 RNA and CD4+ T lymphocyte counts. 
STATISTICAL METHODS 
This is a phase I/II study, and the sample size has not been based on formal power considerations. 
No recruitment limit is set for any of the participating sites, with the only restriction being 
consecutive enrollment that does not exceed 4 subjects per cohort. Subjects for the next cohort will 
not receive busulfan or be infused until the DSMB recommendations are received. 
The primary analysis of safety will be conducted when all recruited subjects have completed 48 
weeks follow-up or have ceased trial follow-up before that time. 
Subject baseline demographic and clinical information will be summarized by treatment group as 
well as overall. There will be no formal comparison of the treatment groups in terms of baseline 
factors (i.e., no p-values). Any subjects discontinuing (i.e. starting antiretroviral or prohibited 


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concomitant medication treatment), or withdrawing (e.g. withdrawing consent to trial follow-up, 
lost to follow-up etc.) will be listed. The time to starting antiretroviral treatment will be summarized 
using Kaplan-Meier plots. 
6DIHW\DQGIHDVLELOLW\DQDO\VHV 
Numbers of individual adverse events, in numbers of subjects, will be summarized by severity and 
treatment, both overall and by nominal study week. Adverse events will also be summarized and 
aggregated by body system for clinical events. The worst severity of each clinical and laboratory 
adverse event for each subject will be summarized by treatment. All grade 3 and 4 adverse events, 
and any other events that lead to subject discontinuation, will be listed by treatment, with duration 
and resolution. 
Feasibility measures will include analysis of the Ttn and HSPCtn release criteria and 
characterization. 
 
 
 
 
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Log10 HIV-1 RNA concentration, lymphocytes (CD4+ T lymphocyte count, CD4+ %, CD4:CD8 
ratio), measures of Cal-1 marking/expression and lymphocyte development (thymopoiesis, 
maturation and inflammation) will be plotted over time for each individual subject, and will be 
summarized for each nominal study week by treatment and overall. Changes in log10 plasma HIV-
1 RNA and CD4+ T lymphocyte count from baseline will be formally compared in all subjects 
using one-sample t-tests or non-parametric equivalents as appropriate. 
Exploratory analyses of log10 plasma HIV-1 RNA, lymphocytes (CD4+ T lymphocyte count, CD4+ 
%, CD4:CD8 ratio), measures of Cal-1 marking/expression and lymphocyte development 
(thymopoiesis, maturation and inflammation)  will use repeated measures ANOVA techniques to 
explore changes from baseline in these endpoints over time, and any differences between treatment 
groups. These analyses are not well powered, and it is accepted they will be exploratory in nature 
and interpreted cautiously. 
3UHOLPLQDU\DQDO\VHV 
There are two planned DSMB safety analyses and one preliminary analysis for safety and 
secondary endpoints at Week 24. The independent DSMB will conduct a complete review of data 
to Week 12 for at least 3 subjects in the preceding Cohort before subjects in Cohorts 2 and 3 receive 
any busulfan and are infused. At each analysis, all subjects’ safety data will be summarized 
including all available data up to the time the analysis is conducted. Measures of Cal-1 
marking/expression will also be summarized. There will be no formal statistical stopping rules, 
rather the study will continue on the basis of there being no evidence of sufficient safety concerns 
to warrant study cessation. The occurrence of bone marrow failure (defined as a protracted 
CCI


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neutropenia (ANC < 0.5x103/µL (mm3)) and/or thrombocytopenia (platelets < 25x103/µL (mm3)) 
after Week 12 post-infusion), the occurrence of grade 4 laboratory abnormalities, unanticipated 
incidence, severity or frequency of AE/SAEs, or failure of Ttn/HSPCtn manufacturing processes 
may be events that could present sufficient safety concerns to warrant study cessation. Efficacy 
indicators, such as the degree of Cal-1 marking in peripheral blood, GALT and bone marrow will 
also be assessed. 
DOSAGE & ADMINISTRATION 
There will be two apheresis stages; the first (1 x 5L) to obtain CD4+ T lymphocytes and the second 
(2 x 15L) to obtain CD34+ HSPC following mobilization with G-CSF (Neupogen®) and plerixafor 
(Mozobil®). The 6 day interval between the first (CD4+) apheresis and commencement of G-CSF 
is to allow hematopoiesis to return to steady state prior to the next procedure. A 5 week (+/-7 days) 
interval between the last apheresis and infusion is in place to give sufficient time for the 
manufacturing steps of transduction, culture and release testing to be completed as well as to allow 
the subject’s bone marrow compartment to return to steady state following the period of 
mobilization. The Cal-1 modified HSPC and CD4+ T lymphocytes will be prepared (cultured and 
transduced) separately and cryopreserved at the completion of the transduction and culture period. 
The following number of cells in the final Cal-1 modified infusion products are anticipated (the 
actual doses being dependent on the numbers of cells harvested by apheresis and yields from the 
laboratory purification, transduction and culture procedures for each individual subject): 
- 
Minimum 2.0x106 cryogenically preserved HSPCtn/kg of body weight with a transduction 
efficiency of ≥ 10% and ≤ 5 copies of the transgene per cell in an approximate volume of 
up to 50ml. 
- 
0.5-20x109 total cryogenically preserved Ttn with a transduction efficiency of ≥ 10% and ≤ 
5 copies of the transgene per cell in a maximum volume of 200ml. 
Each cell type will be thawed and infused following completion of pre-infusion assessments. The 
cellular products will be administered consecutively as intravenous infusions. Subjects will be 
monitored for 2 hours after each infusion for any acute adverse effects. 
A back-up apheresis product containing 1.2x106 unmanipulated CD34+ cells/kg will be available 
for use in the event of delayed hematopoietic recovery and/or bone marrow failure (both as defined 
above).  
 


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TABLE OF CONTENTS 
CONTACT INFORMATION ......................................................................................................... 2 
PROTOCOL SIGNATURE PAGE ................................................................................................. 3 
GLOSSARY OF ABBREVIATIONS ............................................................................................... 4 
SYNOPSIS .................................................................................................................................. 5 
SCHEDULE OF EVENTS – PRE-INFUSION ............................................................................... 13 
SCHEDULE OF EVENTS – POST-INFUSION ............................................................................. 14 
1. 
INTRODUCTION ............................................................................................................. 16 
1.1 
Background 
16 
1.1.1 
Non-clinical studies 
16 
1.1.2 
Clinical studies 
17 
1.2 
Rationale 
22 
2. 
HYPOTHESES ................................................................................................................ 24 
2.1 
Primary Hypothesis 
24 
2.2 
Secondary Hypotheses 
24 
3. 
OBJECTIVES AND OUTCOME MEASURES/ENDPOINTS ................................................. 24 
3.1 
Primary Objective and Outcome Measures 
24 
3.2 
Secondary Objectives and Outcome Measures 
25 
4. 
OVERVIEW OF STUDY DESIGN ..................................................................................... 26 
4.1 
Overview 
26 
4.2 
Design Rationale 
27 
4.2.1 
Pre-infusion Period 
27 
4.2.2 
Post-infusion Follow-up 
28 
4.2.3 
Follow-up Extension 
29 
4.2.4 
Long Term Follow-up 
29 
5. 
TRIAL POPULATION ..................................................................................................... 30 
5.1 
General Considerations 
30 
5.2 
Inclusion Criteria 
30 
5.3 
Exclusion Criteria 
31 
5.4 
Re-screening 
32 
5.5 
Provisions for Repeating Apheresis or Mobilization/Apheresis 
33 
6. 
INVESTIGATIONAL AND CONCOMITANT TREATMENTS .............................................. 33 
6.1 
Investigational Product 
33 
6.1.1 
Physical Description (preparation, handling, packaging, labeling & storage) 
33 
6.1.2 
Treatment Allocation 
35 
6.1.3 
Dosage and Administration 
35 
6.1.4 
Product Quality Incidents 
35 
6.2 
Back-up Apheresis Product 
36 
6.3 
Concomitant Medication and Therapies 
36 
6.3.1 
G-CSF (Neupogen®) 
36 
6.3.2 
Plerixafor (Mozobil®) 
37 
6.3.3 
Busulfan (Busulfex®) 
37 
6.3.4 
Post-busulfan Infection Prophylaxis 
38 
6.3.5 
Antiretroviral Therapy 
39 
6.3.6 
Other on-study concomitant medication and therapies 
39 
7. 
STUDY EVALUATIONS ................................................................................................... 40 
7.1 
Pre Infusion Phase 
40 
7.1.1 
Consent 
40 
7.1.2 
Pre-screening 
40 
7.1.3 
Screening 1 
40 
7.1.4 
Screening 2 
41 
7.1.5 
CD4+ T lymphocyte Apheresis 
42 
7.1.6 
CD34+ Cell Mobilization 
43 
7.1.7 
CD34+ HSPC Aphereses 
44 
7.1.8 
Administration of Busulfan- Cohorts 2 & 3 only 
45 
7.1.9 
Cell Infusion (Day 0) 
46 
 
 


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7.2 
Post Infusion Phase 
47 
7.2.1 
Busulfan Follow-up 
47 
7.2.2 
Weeks 1, 2, & 6 
47 
7.2.3 
Week 4 
48 
7.2.4 
Weeks 8, 16, 20, 28, 36 & 44 
49 
7.2.5 
Weeks 12, 24 & 48 (End of Study) 
49 
7.2.6 
Weeks 32 & 40 
50 
7.2.7 
Follow-up Extension 
50 
7.3 
Safety Evaluations 
51 
7.4 
Feasibility Evaluations 
53 
7.5 
Efficacy Evaluations 
53 
7.6 
Exploratory Evaluations 
55 
7.7 
Specimen storage 
56 
8. 
SUBJECT WITHDRAWAL/DISCONTINUATION .............................................................. 56 
9. 
STATISTICAL METHODS ................................................................................................ 58 
9.1 
Statistical Analyses 
59 
9.2 
Preliminary Analyses 
61 
10. 
ADVERSE EVENT REPORTING ...................................................................................... 62 
10.1 
Adverse Event Definitions and Criteria 
62 
10.1.1  Adverse Event Severity Criteria 
63 
10.1.2  Adverse Event Causality/Association 
63 
10.1.3  Serious Adverse Event 
64 
10.1.4  Serious & Unexpected Suspected Adverse Reaction (SUSAR) 
65 
10.2 
Notification of pregnancy 
66 
11. 
SPECIAL CONSIDERATIONS .......................................................................................... 67 
11.1 
Study-Specific Design Considerations 
67 
11.2 
Ethical and Regulatory Information 
67 
11.3 
Informed Consent 
69 
11.4 
Long Term Follow-up 
70 
11.5 
Privacy and Confidentiality 
70 
12. 
ADMINISTRATIVE CONSIDERATIONS ........................................................................... 71 
12.1 
Subject Screening and Enrollment 
71 
12.2 
Source Documentation 
72 
12.2.1  Documentation of Eligibility 
72 
12.2.2  On-Study Documentation 
72 
12.3 
Case Report Form Completion 
72 
12.4 
Monitoring and Data Quality Assurance 
73 
12.5 
Record Retention 
74 
12.6 
Regulatory Review and Approval Process 
74 
12.7 
Trial Committees 
74 
12.7.1  Medical Review Committee (MRC) 
74 
12.7.2  Data Safety Monitoring Board (DSMB) 
75 
12.8 
Protocol Amendments 
76 
12.9 
Audits 
76 
12.10  Disclosure of Financial Interests 
77 
12.10.1  Sources of Funding and Disclosure of Financial Interest 
77 
12.10.2  Subject Payment and Compensation 
77 
12.11  Use of Information and Publication 
77 
13. 
REFERENCES................................................................................................................. 79 
APPENDIX I ............................................................................................................................. 85 
APPENDIX II ........................................................................................................................... 86 
APPENDIX III ......................................................................................................................... 87 
APPENDIX IV .......................................................................................................................... 91 
APPENDIX V ........................................................................................................................... 94 


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SCHEDULE OF EVENTS – PRE-INFUSION 
 
Weeks relative to CD4+ Apheresis
Days relative to preceding visit (or relative to Day 0) 
 
Can be up to 3 
months prior to 
Screening 1 
≤ 14 
to 
≥ 4
≥ 2 
(weeks after 
Screen 1)
≤ 2
0
+6 
+1
+1
+1
+1
 
 
 
+35
 
 
 
 
 
 
 
 
(≤ -11)
(-4)6
(-2)6
±7 days
ASSESSMENTS 
Consent 
Pre-screening 
(optional) 
Screening 1 
Screening 2 
Pre-apheresis20 
CD4+ 
Apheresis 
G-CSF 1 
G-CSF 2 
G-CSF 3 
G-CSF 4 & Plerixafor 
CD34+ Apheresis 
G-CSF 5  
CD34+ Apheresis 
Pre-busulfan 
Assessment 
Cohort 3: Busulfan 
Administration 
Cohort 2 & 3: Busulfan 
Administration 
Day 0 
Consent 
x
 
Inclusion/exclusion criteria 
x
x
 
Demographics & medical history 
x
x
 
HIV-related history 
x
x
 
Concomitant medications & therapies 
x
x
x
x 
x
x
x
x
x
x
x
x
Adverse events 
x
x
x 
x
x
x
x
x
x
x
x
Physical exam1 
x1
x 
x1
x
Vital signs2 
x
x
x 
x
x
x2
x2
x2
Weight 
x
x 
x
x
x
Venous access assessment 
x
x
 
Chest x-ray 
x
 
Apheresis3 
x
 
x
x
G-CSF 10µg/kg4 
x 
x
x
x
x
Plerixafor 0.24mg/kg5 
 
x5
x
Busulfan administration6 
 
x
x
Infusion of Transduced Cell Products7 
 
x
LABORATORY 
 
Complete blood count with differential9 
x
x
x20
x
x 
x9
x9
x
x
x
Biochemistry10 
x
x
x20
x 
x
x
x
Plasma HIV-1 RNA18 
x
x
x
x
x 
x
x
x
Lymphocyte phenotype (CD3+/CD4+/CD8+) 
x
x
x
x
x 
x
x
Lymphocyte development studies11 
x
 
x
CD34+ enumeration (peripheral blood) 
 
x
x
x
Pregnancy test12 
x
x11 
x11
x11
Pre-screening for co-infection13a 
x
 
Screening for co-infection13b 
x
 
HIV-1 tropism 
x
 
Busulfan pharmacokinetic (PK) monitoring17 
 
x
x
Cal-1 marking/expression analysis – PB14 
 
x
Cal-1 marking/expression analysis – Subsets14 
 
x
Cal-1 integration site analysis 
 
x
Specimen storage15 
 
x
Pre-emptive HLA typing22 
 
x


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SCHEDULE OF EVENTS – POST-INFUSION 
 
 
FOOTNOTES 
1 
Physical examination: Full examinations as indicated. Targeted examination at all other visits. 
2 
Vital signs: Vital signs routinely will involve pulse, blood pressure and temperature measurements, except at busulfan and cell infusion (Day 0) visits, when blood oxygen saturation will also be monitored pre- and 
post-administration of busulfan or cells. 
3 
Apheresis: CD4+ apheresis will be 5L and the CD34+ aphereses will be 15L volumes. 
 
Days post infusion 
Weeks post infusion 
TIME POINT (DAYS | WEEKS) 
Every 
3 
(Wk 1)
7 
Every
3 
(Wk 2)
14 
Every
3 
(Wk 4)
28
Every
3 
6 
8 
12 16
20
24
28
32
36
40
44
48
Early discontinuation / 
withdrawal19 
+4 
WINDOW PERIOD (DAYS) 
±1 
±2 
±1 
±2 
±1 
±2 
±1 
±3 
±3 
±7 
±3 
±3 
±7 
±3 
±3 
±3 
±3 
±3 
±7 
±14 
ASSESSMENTS 
Busulfan F/U16 
 
Busulfan F/U16 
 
Busulfan F/U16 
 
Busulfan F/U16 
 
 
DSMB analysis 
 
 
Preliminary analysis 
 
 
 
 
 
End of study 
Follow-up Extention21 
Concomitant medications & therapies 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x
Adverse events 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x
Physical examination1 
 
x 
 
x 
 
x 
 
x 
x 
x1 
x 
x 
x1 
x 
x 
x 
x 
x 
x1 
x1 
x
Vital signs2 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x
Weight 
 
 
 
 
 
x 
 
 
 
x 
 
 
x 
 
 
 
 
 
x 
x 
GALT biopsy8 
 
 
 
 
 
 
 
 
 
x 
 
 
x 
 
 
 
 
 
x 
x7 
Bone marrow aspirate8 
 
 
 
 
 
 
 
 
 
x 
 
 
x 
 
 
 
 
 
x 
x8 
LABORATORY 
 
 
Complete blood count with differential9, 16 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x
Biochemistry10 
 
x 
 
x 
 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Plasma HIV-1 RNA18 
 
x 
 
x 
 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x
Lymphocyte phenotype (CD3+/CD4+/CD8+)
 
x 
 
x 
 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x
Lymphocyte development studies11 
 
 
 
 
 
 
 
 
 
x 
 
 
x 
 
 
 
 
 
x 
x 
Pregnancy test12 
 
 
 
 
 
 
 
 
 
x 
 
 
x 
 
 
 
 
 
x 
x 
HIV-1 tropism 
 
 
 
 
 
 
 
 
 
x 
 
 
x 
 
 
 
 
 
x 
x 
Cal-1 marking/expression analysis – PB14 
 
x 
 
x 
 
x 
 
x 
 
x 
 
 
x 
 
x 
 
x 
 
x 
x 
x
Cal-1 marking/expression analysis – Subsets14
 
 
 
 
 
x 
 
 
 
x 
 
 
x 
 
 
 
 
 
x 
x19 
Cal-1 integration site analysis 
 
 
 
 
 
 
 
 
 
x 
 
 
x 
 
 
 
 
 
x 
x 
Specimen storage15 
 
 
 
 
 
x 
 
 
 
x 
 
 
x 
 
 
 
 
 
x 
x19 


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4 
G-CSF daily (x 5):10μg/kg QD, commencing day +6, after CD4+ apheresis. The day 4 and 5 dose is to be administered in the morning, prior to visit assessments and apheresis. 
5 
Plerixafor (x1): Single dose of 0.24 mg/kg on Day 4 G-CSF mobilisation. The dose of plerixafor (Mozobil®) is to be administered after apheresis that day, and as late as possible in the day (at least 9 hours, but 
preferably not more than 16 hours prior to the scheduled time of Day 5 apheresis). A second (optional) dose of plerixafor is allowed on the afternoon/evening of Day 3 of G-CSF mobilization, if experience with a 
single dose is not sufficient to achieve desired levels of CD34+ cell harvest. 
6 
Busulfan: The dose of busulfan to be administered is dependent on the cohort to which the subject has been enrolled. Dose is to be based on the subject’s height and current weight (as measured at the Pre-busulfan 
Assessment visit).  Day-4 is for Cohort 3 only. Cohort 2 will receive a single dose of 4mg/kg IV busulfan on Day -2 and cohort 3 will receive two doses of IV busulfan over 3 Days (Days -4 and -2). Cohort 1 will 
not receive any busulfan, so this visit is not applicable to this cohort. Busulfan dosing is always scheduled to complete 2 days prior to the planned cell infusion day (Day 0). 
7  Infusion of Transduced Cell Product: Both CD34+ and CD4+ transduced cell products will be thawed bed-side for immediate infusion. Prior to infusion, viability and sterility will be assessed. For cohorts 2 and 
3, the cell infusions will be 2 days after busulfan administration.  
8 
GALT Biopsy: Gut Associated Lymphoid Tissue Biopsy will be performed to assess Cal-1 marking/expression. A window period of ± 7 days from the time of the visit is permitted for the GALT biopsy. This 
procedure will be performed earlier, as part of the Early Discontinuation/Withdrawal visit, if a subject discontinues prior to the Week 12 visit. If the subject discontinues or withdraws from the study ZLWKLQZHHNV
of the Week 12 or 24 visits (i.e. having already recently undergone the scheduled biopsy), additional GALT biopsies will be included as part of the Early Discontinuation/Withdrawal visit at the discretion of the 
Principal Investigator. 
 
Bone Marrow Aspirate: For Cal-1 marking/expression analysis. A window period of ± 7 days from the time of the visit is permitted for the bone marrow aspirate. This procedure will be performed earlier, as part 
of the Early Discontinuation/Withdrawal visit, if a subject discontinues prior to Week 12 visit. If the subject discontinues or withdraws from the study ZLWKLQZHHNVof the Week 12 or 24 visits (i.e. having already 
recently undergone the scheduled aspirate), an additional bone marrow aspirate will be included as part of the Early Discontinuation/Withdrawal visit at the discretion of the Principal Investigator. 
9 
Complete blood count: Hemoglobin, hematocrit, red blood cell count, white blood cell count including differential and platelet count. Local CBC (in addition to Central Laboratory CBC) will be drawn on both 
G-CSF 4 and G-CSF 4 & Plerixafor CD34+ Apheresis days for safety before proceeding to the next G-CSF dose. 
10 Biochemistry: Non fasting serum biochemistry including electrolytes (bicarbonate, calcium, chloride, magnesium, potassium, sodium), glucose, urea, creatinine/creatinine clearance, creatine phosphokinase (CPK), 
liver function tests (albumin only, total, direct and indirect bilirubin, alkaline phosphatase, GGT, AST/SGOT, ALT/SGPT). 
11 Lymphocyte Development Studies: Extensive phenotypic analysis will be performed to quantify number and percentage of various populations of CD4+ lymphocytes in peripheral blood as a measure of 
thymopoiesis, T-cell maturation, and inflammatory status. 
12 Pregnancy test: serum ȕ-HCG testing of serum from women of reproductive potential, except at commencement of G-CSF, busulfan and cell infusion, when urine test is performed. 
13 a) Pre-screening: Optional Lymphocyte phenotype, HIV-1 RNA, hepatitis B antibody and surface antigen (confirmed by HBV DNA if positive), hepatitis C serology (confirmed by HCV RNA if positive). The 
venous assessment can also be done at this time (or any time after study consent and Screening 1). 
b) Screening: Hepatitis B antibody and surface antigen (confirmed by HBV DNA if positive), hepatitis C serology (confirmed by HCV RNA if positive), West Nile virus RNA, QuantiFERON®-TB Gold/IGRA 
for tuberculosis, HTLV-1/2 and syphilis serology will be performed at screening 1 as part of safety and eligibility checks. Any subject who screens positive for syphilis will not be excluded from the study, but must 
have commenced effective treatment prior to the first apheresis procedure. If a subject completes hepatitis B and/or C co-infection at a pre-screening visit, this testing is repeated again at Screening 1. 
14 Cal-1 marking/expression analysis – PB and subsets: DNA and RNA will be isolated from peripheral blood (PB) and Subsets consisting of purified peripheral blood monocytes, granulocytes, CD4+ and CD8+ 
lymphocytes. 
15 Specimen Storage: Plasma, serum and cryopreserved PBMC. DNA and RNA remaining after scheduled Cal-1 marking/expression and integration analyses will also be retained as part of the stored specimens. 
 
16 Busulfan F/U: For subjects in Cohorts 2 and 3, the busulfan follow up regimen will consist of local CBC/differential (manual differential preferred), vital signs and review for AEs and con-medication changes at 
2-4 day intervals out to Week 6 post infusion.  More frequent or extended follow up may be performed as per PI discretion. 
17 Busulfan PK monitoring: For subjects in Cohorts 2 and 3, blood concentration of busulfan will be measured at pre- and post-infusion time points as described in Appendix IV. 
18 Plasma HIV-1 RNA: A second EDTA plasma sample will be collected and prepared at every time point, except pre-screening, for the purposes of batch analysis with the Abbott m2000 assay. 
19 Early Discontinuation/Withdrawal visit: Blood for the subsets & specimen storage will only be drawn if it has been > 8 weeks since the last subsets blood draw and is anticipated to be > 8 weeks until the next 
scheduled subsets. 
20 Pre-apheresis local labs: Recent CBC/differential and platelets and electrolyte panel is required by apheresis centers for optimization of apheresis collection settings. If the Screening 2 visit is performed  2 
weeks prior to the CD4+ apheresis visit, this visit will not be required. This visit will also be required in event of a repeat manufacturing procedures (refer to Section 5.5). 
21 Follow-up Extension visits: Follow-up visits will continue for any subject who has not commenced ART prior to Week 48, or who has resumed ART but has not achieved a HIV-1 RNA level of < 50 copies/mL 
by Week 48. Any subject who commenced ART and has demonstrated HIV suppression will complete the study at Week 48. 
22 Pre-emptive HLA typing: To be performed prior to busulfan administration, as standard-of-care, according to site collection and laboratory protocols. 
CCI


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1. INTRODUCTION 
1.1 
Background 
It is estimated that 34 million individuals are currently infected with HIV. HIV/AIDS is a 
disease that impairs immune function, primarily by decreasing CD4+ T lymphocytes. The 
progression can be contained by daily dosing with antiretroviral therapy (ART) but there are 
side effects that can be treatment limiting, and the development of HIV drug resistance can 
force the physician to modify the ART regimen. There are no effective vaccines currently 
available for HIV. An alternative approach that could provide a path to a curative therapy is the 
use of cell-derived gene therapy in which an anti-HIV gene(s) is introduced into mature and/or 
hematopoietic stem/progenitor cells (HSPC) to produce a population of white blood cells that 
are protected from the pathogenic effects of HIV-1. This may provide a continuous means of 
controlling HIV-1 after a single or infrequent dose(s). 
The proposed clinical trial is built upon the results of in vitro laboratory studies of Cal-1 and 
the experience in other gene therapy trials for the treatment of HIV-1 and other immunological 
or hematopoietic conditions (Aiuti et al 2002; Kang et al 2002; Malech et al 2004; Barese et al 
2004; Ott et al 2006; Rossi et al 2007; van Lunzen et al 2007; Mitsuyasu et al 2009; Gaspar et 
al 2009; Aiuti et al 2009; Cartier et al 2009; Boztug et al 2010; Cavazzana-Calvo et al 2010; 
Symonds et al 2010).  
1.1.1 
Non-clinical studies 
Pre-clinical safety and efficacy studies have been carried out on human primary cells containing 
the CD4+ and CD34+ target cells. Safety/toxicity studies assessing and analyzing differences 
between Cal-1 transduced and control cells include: 
- 
apoptosis assessment (caspase assays on human primary PBMC); 
- 
proliferation studies (in primary human PBMC); 
- 
cell progenitor skewing assessment (methylcellulose colony progenitor assays on 
CD34+ cells); 
- 
inflammation studies (via IFNTNFand IL-6 ELISA); 
- 
assessment of recombination and replication competent lentivirus (RCL) formation 
of Cal-1. 
None of the above safety/toxicity studies indicated any toxicity risk. 
Efficacy studies analyzing differences between Cal-1 transduced and control cells include: 
- 
MOLT4/CCR5 (immortalized T-cell line) HIV-1 challenge assays with a variety of 
laboratory strains; 


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- 
PBMC HIV-1 challenge assays with a variety of HIV-1 laboratory and primary 
isolate strains; 
- 
Real Time quantitative RT-qPCR assays (RNA expression) using PBMC to assess 
C46 expression. 
- 
Flow cytometric analyses (FACS) using PBMC and T-cell lines to assess the protein 
expression levels of CCR5 and C46. 
- 
Ex vivo efficacy study using hu-NSG (BLT) mice. Splenocytes isolated from BLT 
mice generated with Cal-1 transduced CD34+ HSPC were isolated and challenged 
ex vivo with either R5 tropic HIV (BaL) or X4 tropic HIV (NL4-3). These cells 
were found to be protected from both R5- and X4-tropic HIV-1 infection. 
In vivo studies 
Safety and efficacy studies have been carried out using animal models.   
- 
In vivo safety and toxicity in humanized murine model. The study did not detect any 
safety or tolerability issues for the human fetal liver CD34+ cells transduced with 
Cal-1 in NSG murine test system. 
- 
In vivo efficacy in humanized BLT mice. Animals treated with Cal-1 transduced 
human CD34+ HSPC were challenged with high dose of R5-tropic BaL HIV-1. 
Treated animals displayed a profound reduction in HIV infection, as well as stable 
marking of Cal-1 expression. 
- 
In addition, safety and efficacy study in non-human primates, is currently underway. 
The efficacy results indicate that an MOI between 1 and 5 leads to a copy number between 1 
and 2 of the therapeutic target and expression of the therapeutic sequences (as determined by 
quantitative real time PCR for C46). Moreover, HIV-1 challenge assays demonstrate protection 
against a range of laboratory and primary isolates. 
1.1.2 
 Clinical studies 
Gene therapy approaches to the treatment of HIV-1 have included a variety of viral and cellular 
targets. Although clinically significant efficacy has yet to be established, the feasibility of gene 
therapy as a therapeutic approach was established in a phase II clinical trial involving 74 gene 
therapy recipients in two countries (Mitsuyasu et al 2009 and 2011). The clinical potential of 
gene therapy as a treatment for HIV-1 has also been realized with the ‘Berlin patient’ who 
received an allogeneic bone marrow graft homozygous for the CCR5 32 mutation in 
conjugation with myeloablation for leukemia treatment (discussed further below). Collectively, 
experience to date has shown the feasibility and clinical potential of the approach. 
Our approach seeks to protect CD4+ T lymphocytes and/or CD34+ HSPC progeny, from HIV-
1 by reducing the expression of the HIV-1 co-receptor CCR5 and blocking fusion of HIV-1 to 


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the cell membrane through expression of the C46 peptide. Clinical data available to date on 
these two targets is discussed below. 
CCR5 
Genetic modulation of CCR5 for HIV-1 therapy has a strong theoretical basis. Individuals with 
naturally occurring mutations in CCR5 (CCR532) are protected from HIV-1 infection and 
disease progression. Heterozygous individuals with only a 50% reduction of CCR5 cell surface 
expression have substantially reduced disease progression rates (Ioannidis et al 2001; O’Brien 
and Nelson 2004). A recent report has shown that allogeneic transplantation of CCR532 
HSPC eliminated detectable levels of HIV-1 and may be curative (Hütter et al 2009; Allers et 
al 2011). As treatment for acute myeloid leukemia, the HIV+ patient underwent myeloablative 
conditioning and received a graft containing 2.3x106 CD34+ cells (with the 32 mutation) per 
kg of body weight, followed by a second transplant of 2.1x106 CD34+ cells per kg from the 
same donor approximately 1 year later. Prior to the transplant, sequence analysis identified that 
the patient carried HIV variants with predominantly CCR5 co-receptor tropism and only 2.9% 
CXCR4 and dual-tropic variants. ART was discontinued on the day of the initial transplant and 
HIV-1 RNA and proviral DNA remained undetected in peripheral blood, bone marrow and 
rectal mucosa 20 months post-transplant (Hütter et al 2009), and no replication-competent virus 
could be cultured from PBMCs (Yukl et al 2013). 5 years post-transplantation, the patient 
remained off ART, CD4+ T-cell count had increased and plateaued within the normal range 
and HIV-1 RNA and DNA had remained undetectable in plasma and PBMCs respectively 
(Allers et al 2011). The absence of recrudescent HIV replication and waning HIV-specific 
immune responses five years after withdrawal of treatment has been reported (Yukl et al 2013). 
In 2010, Sangamo Biosciences Inc. commenced a Phase I clinical trial of CCR5 Zinc Finger 
Nuclease (ZFN)-modified autologous CD4+ T lymphocytes in HIV-1 infected subjects 
(clinicaltrials.gov, NCT01044654). This study is ongoing and while there have been 
presentations at meetings, results have not yet been published. Pre-clinical in vitro and mouse 
studies have demonstrated generation of CD4+ T lymphocytes that are resistant to HIV-1 
infection by disruption of endogenous CCR5 through engineered zinc-finger nucleases (CCR5 
ZFNs) delivered by the adenoviral vector Ad5/35 (Perez et al 2008; Holt et al 2010). NOG 
mice that received primary human CD4+ T lymphocytes transduced with the Ad5/35 CCR5 
ZFNs showed a significantly lower plasma HIV-1 viremia compared to the control mice after 
50 days and a 3-fold enrichment of the CCR5 ZFN-modified human CD4+ T lymphocytes after 
30 days. These results suggested that the infusion of ex vivo expanded CCR5 ZFN-modified 
autologous CD4+ T lymphocytes may be a safe and viable approach to the treatment of HIV-1 
infection. 
The first approved drug on the market targeting CCR5, Maraviroc, (Dorr et al 2005), is a 
small molecule inhibitor that antagonizes CCR5 and prevents HIV-1 entry into cells; it was 


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approved by the US FDA in 2007 for treatment-experienced patients and later in 2009 for 
treatment-naïve  patients. 
C46 
HIV-1 fusion inhibitors either inhibit the first step of membrane fusion; the insertion of the viral 
fusion peptide into the target cell membrane, or prevent the subsequent six-helix bundle 
formation. The N and C peptides belong to the latter group and are derived from the highly 
conserved amino acid sequences of the N and C heptad repeats of gp41, respectively. Several 
C peptides have been described, the most prominent family member being T20 (C36, 
enfuvirtide or Fuzeon®), which was the first entry inhibitor approved for clinical treatment of 
HIV-1 infection (Cervia and Smith 2003). T20 is a synthetically produced soluble peptide of 
36 amino acids representing a portion of the natural sequence of the gp41 HR2 of HIV-1 (Wild 
et al, 1994). In clinical Phase III trials, an optimal dose of 100 mg enfuvirtide (T20) twice daily 
resulted in a clearly reduced viral load (two logs) and an increase in the patients’ CD4 cell count 
(Kilby et al 1998). However, the peptide is not orally bioavailable and thus has to be injected 
subcutaneously twice per day. It also has a very short serum half-life of only 2-4 hours, which 
is the reason for the high peptide dose, leading to a therapy cost of approximately $20,000 per 
patient per year. Another major problem of enfuvirtide treatment is the rapid emergence of 
resistant virus variants with monotherapy (Rimsky et al 1998). Another C-peptide, Sifuvirtide, 
designed on the basis of the three-dimensional structure of the HIV-1 gp41, was tested recently 
in a phase IIb clinical trial (reviewed in Yu et al 2013). 
Several novel C peptides are also active against viruses that are resistant to enfuvirtide. These 
C peptides are elongated at the amino terminus and interact with a highly conserved 
hydrophobic groove at the C-terminus of the central N heptad repeat coiled-coil structure (T-
1249, C46). 
There is strong pre-clinical data in tissue culture and animal models that C46 is very efficient 
at inhibiting HIV-1 replication and its pathogenic effects (Egelhofer et al 2004; Zahn et al 2008, 
Younan et al 2013). C46 expressed on transduced CD4+ T lymphocytes were introduced into 
HIV+ subjects in a Phase I clinical trial and was shown to be safe with ongoing detection of 
gene-marked cells (van Lunzen et al 2007). In a Phase I clinical trial of 10 advanced HIV+ 
subjects who received T lymphocytes transduced with a retroviral vector that expressed the 
entry-inhibiting peptide, maC46, gene-modified cells could be detected in the peripheral blood, 
lymph nodes and bone marrow throughout a 1 year follow up period, with marking levels 
correlating to the transduced cell dose (van Lunzen et al 2007). After CD8+ depletion, the 
remaining cells were cultured, transduced and expanded over a maximum total period of 13 
days before cryopreservation for later infusion. The 10 subjects received an infusion of between 
3x109 to 17x109 CD8-depleted T lymphocytes, with an average of 1x109 of these containing 
the gene vector. 


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As the gene modification coded for production of a receptor on the cell surface, subjects were 
monitored for a possible immune response against the gene-modified cells. Titers of antibodies 
against maC46 remained stable or even declined during the first months after infusion, and 2 
subjects who were maC46 sero-negative pre-infusion did not seroconvert post-infusion, 
indicating that a humoral immune response against the maC46 peptide produced by the gene-
modified T lymphocytes was unlikely (van Lunzen et al 2007). 
Busulfan 
Despite relatively high numbers of CD34+ HSPC and their efficient ex vivo transduction, when 
the cells are re-introduced into the subject, the number of HSPCtn that home to, and engraft in, 
the bone marrow (as measured by peripheral blood marking) appears to be generally low. The 
reasons for this are not well understood, but one obstacle may be the space available in the stem 
cell compartment (the bone marrow) for the engraftment of the new, modified HSPC. Thus 
creating an environment that enhances the ability of the modified cells to engraft and 
significantly contribute to the hematopoietic regeneration, either by a natural survival 
advantage (as occurs with some genetic immunodeficiencies) or through myeloablation, may 
be a crucial element in successful engraftment and expression of gene-modified CD34+ HSPC. 
Busulfan is indicated for use in conditioning regimens prior to allogeneic hematopoietic 
stem/progenitor cell reconstitution for the treatment of hematologic malignancies and 
increasingly used in non-malignant conditions, such as autoimmune disease (Burt et al 2008). 
For myeloablation of adults, busulfan (16 doses of 0.8mg/kg) is often used in conjunction with 
cyclophosphamide. A moderate dose of 8 to 10mg/kg busulfan with fludarabine is used to 
achieve reduced intensity conditioning and low dose busulfan (3.2mg/kg) with fludarabine is 
used in non-myeloablative transplantation (Alyea et al 2005; Lim et al 2010; Shi et al 2013). 
The use of single dose busulfan as a conditioning agent prior to infusion of genetically modified 
autologous HSPC has not been established clinically, however there are precedents for the use 
of conditioning regimens within the area of gene therapy. 
Low dose busulfan administered in the context of gene transfer for ADA-SCID has shown 
transient myelosuppression without organ toxicity (Aiuti et al 2002). Since 2000, a total of 15 
pediatric patients with ADA-SCID have received ADA genetically modified CD34+ HSPC 
following 
non-myeloablative 
preconditioning 
with 
2mg/kg/day 
busulfan 
delivered 
intravenously at 3 and 2 days prior to infusion (Gaspar et al 2009; Aiuti et al 2002; Aiuti et al 
2009). To provide further selective advantage for the ADA-transduced cells, PEG-ADA 
enzyme replacement therapy was not given after infusion of the gene modified CD34+ HSPC. 
The study participants were aged between 0.6 to 5.6 years of age, and published data out to a 
median of 4 years demonstrates that the gene therapy delivered in conjunction with the reduced 
intensity conditioning regimen is a safe and effective treatment for ADA-SCID affected 
children and that the use of the non-myeloablative conditioning (along with withdrawal of PEG-
ADA) was crucial in achieving clinically significant outcomes (Aiuti et al 2009). In a recent 


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study, 10 ADA-SCID pediatric patients, aged between 15 months and 20 years received 
intravenous infusion of gene-modified autologous bone marrow CD34+ cells. Four subjects 
received the modified cells without conditioning, while 6 subjects were administered between 
1.9-4.9mg/kg busulfan on two successive days before infusion of the gene-corrected cells. The 
study demonstrated that the group receiving busulfan had no clinical toxicities related to the 
conditioning, and that busulfan led to substantial levels of gene-corrected T-lymphocytes 
expressing ADA enzyme activity (Candotti et al 2012). 
In 2 subjects with chronic granulomatous disease (CGD) who received non-myeloablative 
busulfan conditioning prior to transplantation of genetically modified CD34+ cells, Ott and 
colleagues reported sustained engraftment of functionally corrected cells that produced 
therapeutically relevant levels of superoxide (Ott et al 2006). In this study, liposomal busulfan 
at a dose of 4mg/kg was administered intravenously every 12 hours at 3 and 2 days prior to the 
transplant. The dose and conditioning regimen was reportedly well tolerated, with no serious 
adverse events. A period of myelosuppression with absolute neutrophil counts below 500 
cells/µl and CD4+ T lymphocyte counts below 200 cells/µl was observed in both subjects for 
out to 32 days post transplantation. Both cell counts gradually recovered within 2 to 3 months 
to normal values (P1, 476 CD4+ cells/ml; P2, 313 CD4+ cells/ml) observed before G-CSF 
mobilization and busulfan conditioning (Ott et al 2006). Previous attempts to correct human 
CGD by gene therapy in the absence of bone marrow ablation have been unsuccessful (Malech 
et al 2004; Barese et al 2004). In a brief report, an 8.5 years old X-linked CGD child received 
busulfan conditioning of 8.8 mg/kg intravenously, and CD34+ gene marked ex-vivo. The 
patient experienced a short period of myelosuppression, followed by hematopoietic 
reconstitution and gene marking (Bianchi et al 2009).  In a recent report, Malech and colleagues 
have treated 3 X-linked CGD adult patients with a higher, but still not ablative dose of busulfan 
(10mg/kg total dose) followed by autologous CD34+ transduced ex vivo with a retroviral vector 
encoding gp91phox. The busulfan conditioning was well tolerated by all patients and it was 
reported to greatly improve initial marking and resulted in persistence of marking in 2 of the 3 
patients (Kang et al 2010). 
The successful use of busulfan as a conditioning agent in the experimental transplant of 
genetically modified CD34+ cells for other genetic abnormalities such as Wiskott-Aldrich 
syndrome (Boztug et al 2010), X-linked adrenoleukodystrophy (ALD) (Cartier et al 2009) and 
β-Thalassemia (Cavazzana-Calvo et al 2010) has also been reported. Boztug and colleagues 
administered a busulfan dose of 4mg/kg per day 3 and 2 days prior before infusion. Transient 
myelosuppression and partial alopecia were observed as busulfan-associated side effects 
(Boztug et al 2010). 
More intensive conditioning regimens for transplantation of genetically modified CD34+ cells 
have also been recently reported. A myeloablative regimen of cyclophosphamide and busulfan 
was justified by Cartier and colleagues for use in the treatment of ALD because the genetically 


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modified CD34+ cells were not anticipated to have any selective growth advantage. In the 2 
pediatric subjects, sustained hematopoietic recovery was reported 13-15 days post infusion 
(Cartier et al 2009). Likewise, with the aim to eliminate diseased hematopoietic stem cells in 
β-Thalassemia, Cavazzana-Calvo and colleagues administered intravenous Busulfex® 
(3.2mg/kg/day for 4 days) without the addition of cyclophosphamide before infusion of 3.9x106 
cryopreserved genetically modified CD34+ cells per kg (Cavazzana-Calvo et al 2010). This 
intensive pre-transplant conditioning appears to have been well tolerated, with uneventful 
hematopoietic reconstitution reported. In both studies, the degree of pre-transplant conditioning 
appears to have been a crucial factor in the clinical outcomes observed. 
Approximately 100 HIV+ patients with lymphomas have been treated with autologous 
peripheral stem cell transplant using various conditioning regimens that have included the 
alkylating agents busulfan, cyclophosphamide, carmustine and/or melphalan (Michieli et al 
2011). A multicenter AIDS Malignancy Consortium trial treated 20 patients who had recurrent 
and extensively chemotherapy pretreated HIV-associated non-Hodgkin’s lymphoma or 
Hodgkin’s lymphoma with a dose-reduced busulfan and cyclophosphamide preparative 
regimen with autologous stem cell transplantation (Spitzer et al 2008). The majority of subjects 
received a total dose of 11.2mg/kg intravenous busulfan over 3.5 days (14 doses of 0.8mg/kg 
every 6 hours) followed by 120mg/kg cyclophosphamide over 2 days for subjects 50 years of 
age or older. Baseline viral load ranged between 50 to 5712 copies/ml and CD4+ T-cell counts 
between 53 and 574 cells/µl. CD4+ T-cell counts and viral load were measured at 2 and 3 weeks 
and at months 1, 2, 3, 6, 9, and 12 post-transplant. The conditioning regimen did not appear to 
have a consistent effect on these measures of HIV activity and appeared to be well tolerated in 
the patient group (Spitzer et al 2008). One serious adverse event related to the conditioning 
regimen was reported in a subject who developed post-transplant hepatic veno-occlusive 
disease at day +12 that resulted in death due to multi-organ failure at day +33. Non-
myeloablative conditioning with cyclophosphamide and fudarabine has been successful in 
conditioning 2 HIV+ patients for allogeneic CD34+ cell transplantation, including 1 subject 
who received gene-modification with a HIV-resistant vector carrying a dominant-negative 
mutant Rev (Kang et al 2002). 
1.2 
Rationale 
Our approach aims to protect CD4+ T lymphocytes and/or CD34+ HSPC progeny from HIV-1 
by reducing the expression of the HIV-1 co-receptor CCR5 and blocking fusion of HIV-1 to 
the cell membrane through expression of the C46 peptide. Clinical studies, meta analyses, and 
case reports described above support the rationale that CCR5 is an excellent target for gene 
therapy-mediated gene silencing. It is well known that HIV-1 can rapidly develop resistance to 
monotherapy. We therefore are also using a second gene therapeutic agent, a HIV-1 fusion 
inhibitor termed C46 that blocks entry of the virus. The vector termed Cal-1 encodes both a 
shRNA to CCR5 (termed sh5) (Qin et al 2003; An et al 2006; An et al 2007; Shimizu et al 2009; 


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Liang et al 2010; Shimizu et al 2010) and the C46 peptide (Egelhofer et al 2004; Perez et al 
2005; Schambach et al 2006; van Lunzen et al 2007; Zahn et al 2008; Trobridge et al 2009; 
Kimpel et al 2010), within a single self-inactivating lentiviral vector. 
The short hairpin RNA against the HIV-1 co-receptor CCR5 (sh5) is driven by the H1 promoter, 
and the HIV-1 fusion inhibitor, C46 is driven by the ubiquitin C promoter. Once integrated into 
the target cell, sh5 produces an siRNA that reduces the expression of CCR5 on the cell surface. 
The additional C46 component codes for production of a membrane-anchored C-peptide 
derived from the HIV-1 envelope glycoprotein gp41 (Zahn et al 2008). The peptide is expressed 
on the surface of the transduced cell and acts as a HIV-1 fusion inhibitor. 
 
Because the progression of HIV infection depletes CD4+ T cells, the Ttn treatment is included 
in addition to the HSPCtn to rapidly replenish the immune system with disease-resistant T cells 
and provide a short to medium term effect. CD4+ memory/effector T cells migrate mostly 
through the peripheral tissues and have been observed to persist in vivo for several years and 
have the capability for self-renewal (Perez et al 2008; Sallusto et al 1999). Early clinical data 
in the field of gene therapy for genetically or acquired immunodeficiency and metastatic 
melanoma show that delivery of genetically modified CD4+ T lymphocytes is safe and the 
modified cells can have a survival advantage and sustained engraftment (Deeks et al 2002; 
Frecha et al 2010; Humeau et al 2004; June 2011; Kreeger 2010; Levine et al 2002; Levine et 
al 2006; Levine 2008; Macpherson et al 2005; Mitsuyasu et al 2000; Morgan et al 2005; Ranga 
et al 1998; Podsakoff 2005; Tebas 2010; van Lunzen et al 2007; Muul et al 2003; Morgan et 
al 2006; Edelstein et al 2007; Scholler et al 2012) and suggests potential for a prolonged clinical 
effect. 
We have conducted preclinical experiments that show the harvested CD4+ T lymphocytes and 
mobilized/harvested CD34+ HSPC can be cultured ex vivo and effectively transduced with Cal-
1 to yield sufficient numbers of viable, sterile cell populations for intravenous infusion. Once 
transduced with Cal-1, CD4+ T lymphocytes (Ttn) and the CD34+ HSPC (HSPCtn) progeny 
will be protected from HIV-1 infection and its pathogenic sequelae. This protective effect may 
act to lower HIV-1 RNA and increase CD4+ T lymphocyte counts in the individual, thereby 
decreasing or delaying (partially or completely) the need for antiretroviral therapy. 


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2. HYPOTHESES 
2.1 
Primary Hypothesis 
In subjects with HIV-1 infection that have previously received treatment with antiretroviral 
agents, delivery of HSPCtn and Ttn has the potential to be a safe and feasible means to reduce 
HIV-1 RNA and increase CD4+ T lymphocyte cell counts (as compared to a Pre-Busulfan  
Assessment visit baseline) in the absence of other antiretroviral therapy. 
2.2 
Secondary Hypotheses 
In subjects with HIV-1 infection that have previously received treatment with antiretroviral 
agents: 
- 
HSPCtn will home to the bone marrow, engraft and provide a population of peripheral 
blood hematopoietic cells protected from HIV-1. 
- 
Intravenous busulfan will facilitate re-engraftment of HSPCtn in the bone marrow, 
resulting in increased levels of Cal-1 marking in the bone marrow, GALT and peripheral 
blood, compared to the non-busulfan cohort. 
- 
Ttn will be protected from the pathogenic effects of HIV-1 and provide a short to 
medium term replenishment of CD4+ T lymphocytes in the peripheral blood. 
3. OBJECTIVES AND OUTCOME MEASURES/ENDPOINTS 
This protocol is a first in human study of Cal-1 modified CD4+ and CD34+ hematopoietic cells, 
and is designed to detect and characterize acute, sub-acute and medium term safety considerations 
and toxicities of Cal-1 and the associated delivery procedures. Additionally, the following data will 
be assessed to provide evidence required to consider larger scale phase II evaluation of Cal-1: 
- 
Cal-1 marking/expression by PCR in peripheral blood, bone marrow and GALT to assess 
the distribution, percentage contribution and expansion of HSPCtn and Ttn. 
- 
Assessment of lymphocyte development through analysis of thymopoiesis and maturation 
markers in peripheral blood to determine if thymic production is active. 
- 
Assessment of chronic inflammatory status through analysis of inflammation markers on 
peripheral blood lymphocytes. 
- 
Plasma HIV-1 RNA and lymphocyte phenotyping (CD4+ T lymphocyte count, percentage, 
and CD4+:CD8+ ratio) to assess the potential impact on HIV-1. 
- 
Development of potential resistance by a tropism shift from R5 to dual/mixed or X4. 
3.1 
Primary Objective and Outcome Measures 
To evaluate in HIV-1 infected adults who have previously been on ART: 
- 
The safety and feasibility of the introduction of Cal-1, gene-transduced, hematopoietic 
cell populations. 


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- 
The safety of intravenous busulfan as a means to improve HSPCtn engraftment. 
Safety outcomes up to study completion will be measured according to the safety evaluations 
described in section 7.3. Feasibility measures will include the number of Ttn and HSPCtn 
manufacturing procedures successfully completed (i.e. complying with all release criteria), 
CD4+ and CD34+ purity, expression of various surface markers, and the number of target cells 
harvested. 
3.2 
Secondary Objectives and Outcome Measures 
To assess the difference between the 3 treatment cohorts in: 
1. The extent of HSPCtn contribution and Ttn survival by evaluation of Cal-1 marking and 
expression in peripheral blood at time points up to study completion or discontinuation. 
2. The extent of HSPCtn contribution and Ttn survival by evaluation of Cal-1 marking and 
expression in gut-associated lymphoid tissue (GALT). 
3. The potential benefit of busulfan conditioning as determined by;  
a. The extent of engraftment and differentiation of HSPCtn over time by evaluation of 
Cal-1 marking and expression in peripheral blood subpopulations (monocytes, 
granulocytes, CD4+ and CD8+ lymphocytes)  
b. The extent of HSPCtn engraftment by evaluation of Cal-1 marking and expression 
in bone marrow at Week 12 
4. The potential efficacy of Cal-1 in controlling HIV-1 infection for each subject, as measured 
by: 
a. Plasma HIV-1 RNA relative to the Pre-busulfan Assessment visit 
b. Plasma HIV-1 RNA over time 
c. CD4+ T lymphocyte count, percentage and CD4+/CD8+ T lymphocyte ratio relative 
to the Pre-busulfan Assessment visit 
d. CD4+ T lymphocyte count, percentage and CD4+/CD8+ T lymphocyte ratio over 
time 
e. Time to commencement of antiretroviral therapy (as defined in Section 6.3.5) 
The endpoint for these analyses is study completion, withdrawal, or until discontinuation 
due to secondary analysis endpoint criteria (as defined in sections 8 and 9). 
5. Impact on lymphocyte development for each subject, as measured by changes in 
thymopoiesis, maturation and inflammation markers in peripheral blood relative to pre-
infusion baseline over time. 
6. A tropism shift from R5 to dual/mixed or X4 at any time point post-infusion. 


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4. OVERVIEW OF STUDY DESIGN 
 
4.1 
Overview 
This is an adaptive design, open-label pilot study to evaluate the safety and feasibility, and 
preliminary indications of efficacy of Cal-1 in HIV-1 infected adults who have a history of 
previous treatment with ART but are no longer receiving ART. It is planned that up to 12 
subjects will be enrolled, at least 3 subjects per each of 3 possible cohorts. One of the critical 
factors affecting potential efficacy is engraftment of the gene-modified HSPC in the bone 
marrow. Through the adaptive enrollment of 3 cohorts, the study aims to evaluate the safety 
and tolerability of busulfan as a pre-infusion conditioning agent to optimize engraftment, 
subsequent expression and efficacy in affording protection against progression of HIV-1 
infection. 
Cohort 1 will enroll subjects, who will undergo CD4+ T lymphocyte apheresis and CD34+ 
HSPC mobilization, apheresis and infusion procedures without any busulfan conditioning. At 
Week 12 post-infusion for the third subject in Cohort 1, acute and sub-acute adverse effects, as 
well as indications of Cal-1 engraftment (marking within bone marrow, peripheral blood and 
GALT) will be assessed by an independent Data Safety Monitoring Board (DSMB). With 
DSMB approval the study will then continue with Cohort 2, who will undergo identical 
procedures with the exception of pre-infusion conditioning with a single dose of 4mg/kg 
busulfan 2 days prior to infusion. Similarly, at 12 weeks post infusion for the third subject in 
Cohort 2, the DSMB will compare the acute and sub-acute adverse events and indications of 
Cal-1 engraftment of Cohort 2 against Cohort 1 to assess the effects of busulfan on the early 
outcomes and if the data suggest: 
- 
there is favorable benefit relative to risk for the use of busulfan; and/or 
- 
a higher dose (8 or 6 mg/kg busulfan) may result in further benefits with respect to 
potential engraftment and peripheral expression 
The DSMB may recommend a number of possible adjustments with respect to the dosing with 
busulfan in Cohort 3: 
- 
continue non-conditioning protocol without the use of busulfan 
- 
continue to use a single 4mg/kg dose of busulfan at Day -2 


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- 
proceed using a dose (8, 6 or 4 mg/kg busulfan) administered as two doses of 4, 3 or 2 
mg/kg QD completing 2 days prior to infusion 
4.2 
Design Rationale 
4.2.1 
Pre-infusion Period 
Because of the logistical considerations with scheduling the pre-infusion procedures, subjects 
may sign consent and have pre-screening performed up to 3 months prior to the first procedure 
of the Screening 1 visit. Additionally, concurrent screening of potential subjects is permitted 
within the limitation described in Section 12.1. 
Two screening visits are performed to allow confirmation of the potential subject’s plasma 
HIV-1 RNA and CD4+ T lymphocyte count.  
The first apheresis procedure is for the collection of CD4+ T lymphocytes. Subjects will 
undergo a 5L apheresis following completion of all other assessments scheduled to occur at that 
study visit. It is anticipated that apheresis will yield 2.5 to 5x108 CD4+ T lymphocytes in total. 
The apheresis volume may be adjusted during the study to yield the desired cell number.  
Subjects will receive 10µg/kg QD G-CSF (Neupogen®) as a subcutaneous injection over 5 
consecutive days, starting 6 days after the CD4+ apheresis. The 6 day period between the 
lymphocyte apheresis and the first dose of G-CSF is to allow hematopoiesis to return to steady 
state before mobilization commences. 
Regarding the second set of apheresis procedures. previous clinical trial data has shown that 
large volume apheresis (20L) on 2 consecutive days yielded a mean infused CD34+ cell dose 
of 9x106 CD34+ cells/kg body weight, but also resulted in a protracted period of 
lymphodepletion (Mitsuyasu et al 2009). Thus far, a single 20L apheresis has yielded a mean 
of 2.2x106 CD34+ HSPCtn/kg (Cohorts 1 and 2). In Cohort 3, subjects will undergo two 15 L 
aphereses. It is estimated that this volume of apheresis, on Days 4 and 5 of mobilisation, will 
yield adequate CD34+ HSPCs to consistently manufacture the minimum desired HSPCtn dose 
of 2.0x106 cells/kg, without significant depletion of other peripheral blood components 
(Anderlini et al 1996).  
In the event that the manufactured yield of HSPCtn using this CD34+ mobilisation regimen and 
2x15 L aphereses is <2.0x106 HSPCtn/kg, the existing HSPCtn product will be stored and the 
subject given the option for repeat CD34+ mobilisation and apheresis (refer to Section 5.5). 
Additionally, if the HSPCtn yield using the above CD34+ mobilisation/apheresis regimen is 
<2.0x106 HSPCtn/kg, this will trigger a review of the mobilisation regimen by the study MRC. 
The review will consider an extra 0.24 mg/kg dose of plerixafor to be administered by 
subcutaneous injection on Day 3 of G-CSF dosing (as well as Day 4) (refer to Section 6.3.2). 


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Urine pregnancy tests are scheduled to be performed before the commencement of G-CSF and 
again before busulfan and infusion to confirm that a female subject of child-bearing potential 
has not become pregnant during the pre-infusion study phase. 
The 5 week (+/- 7 days) interval between the final CD34+ apheresis and infusion is to allow 
time for: 
- 
All manufacturing steps of transduction, culture and release testing to be completed. 
- 
The subject’s bone marrow to restore to steady state following the period of CD34+ 
cell mobilization and apheresis. 
The use of intravenous busulfan prior to infusion of the HSPCtn is as a reduced intensity regimen 
designed to have a non-myeloablative conditioning effect. Based on the available clinical and 
pre-clinical information, the following doses of Busulfex® were chosen for this study: 
- 
4mg/kg single dose, which represents approximately one-third of the total 
myeloablative dose, and is comparable with published experience that reports 
enhancement of engraftment of gene modified CD34+ cells with minimal toxicity and 
no long term adverse effects. 
- 
6 to 8mg/kg (3 to 4mg/kg QD for 2 days), which is a moderate dose equivalent to that 
previously administered to CGD patients (Ott et al 2006). 
Different doses are being assessed to potentially identify the minimum effective dose to safely 
facilitate engraftment without being myeloablative. Pharmacokinetic analysis will be 
performed on plasma samples (refer to Appendix IV for details). Progression to each cohort is 
dependent on the recommendation of the DSMB, based on safety and secondary efficacy data 
from cohorts 1 and 2. 
During the Pre-busulfan Assessment visit, all subjects in Cohort 3 will have pre-emptive HLA 
genotyping and/or serotyping from peripheral blood samples collected according to the site’s 
internal standard-of-care protocol(s). This is to facilitate a rapid transition to standard-of-care 
clinical treatment(s) – including possible allogeneic transplantation – in the unlikely event of 
sustained bone marrow failure that is unresponsive to treatment with G-CSF and/or infusion of 
the back-up, unmodified 1.2x106 CD34+ cells/kg apheresis product.  
4.2.2 
Post-infusion Follow-up 
Routine subject monitoring will be performed weekly for the first 2 weeks and then every 
second week until 2 months post-infusion, extending to 4-weekly intervals to Week 48. After 
this time, subjects may continue follow up for up to one additional year (refer to Section 4.2.3). 
During the post-infusion period, subjects in each cohort will remain off ART unless confirmed 
CD4+ T lymphocyte counts, CD4+ T lymphocyte percentage, or plasma HIV RNA values reach 
the safety limits, or other criteria, specified in Section 6.2.4.  


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Post-busulfan follow-up will be performed more frequently (per the post-infusion schedule of 
events) for at least 6 weeks post-infusion. More frequent or extended follow up may be 
conducted if clinically indicated (per Section 7.2.1 Conditioning Follow Up). 
Cal-1 marking/expression data obtained from peripheral blood mononuclear cells will provide 
information on the survival of Cal-1 containing cells over time, but it will not be possible to 
differentiate if these are derived from the HSPCtn or Ttn populations. Analysis of CD8+ 
lymphocyte, monocyte and granulocyte fractions will be informative as to the contribution from 
HSPCtn. Additionally, bone marrow aspirates at 12, 24 and 48 weeks’ post-infusion (each ± 1 
week) will enable assessment of the extent of engraftment of Cal-1-containing cells in the bone 
marrow. This will be used to evaluate the potential benefits and risks of a reduced intensity 
busulfan conditioning regimen. A maximum bone marrow volume of 10ml will be collected. 
The whole bone marrow aspirate will be for Cal-1 marking and expression analysis. 
A substantial proportion of the body’s total CD4+ T lymphocytes reside in the gastrointestinal 
mucosa (Allers et al 2011). A rectal gut-associated lymphoid tissue (GALT) biopsy will be 
obtained at 12, 24 and 48 weeks’ (each ± 1 week) post-infusion in order to obtain a number of 
small tissue specimens for the purposes of Cal-1 marking and expression level analysis. 
All enrolled subjects will be followed for a maximum period of 48 weeks post-infusion. If a 
subject should withdraw consent, they will be asked to continue in long term follow-up.  
Any subject who meets any one of the discontinuation criteria will continue study visits per the 
schedule of events. In the event a subject discontinues or meets a secondary analysis endpoint 
criteria prior to Week 12, the GALT biopsy and bone marrow aspirate will be performed, if 
possible, at the time of discontinuation, or the next earliest time point. If a subject discontinues 
post-Week 12, an additional GALT biopsy and bone marrow aspirate will be performed if 
possible, providing eight weeks has elapsed since the last biopsy/aspirate. 
4.2.3 
Follow-up Extension 
At Week 48, subjects who remain off ART will continue to have HIV and general health 
monitoring at monthly intervals (± 2 weeks) until confirmed CD4+ T lymphocyte counts, CD4+ 
percentage of total lymphocytes, or plasma viral load values reach pre-specified safety limits, 
or other criteria, as described in Section 6.3.5. Subjects will continue to be monitored for up to 
one year, or until ART is commenced and HIV-1 RNA levels of < 50 copies/mL are achieved 
(whichever occurs first). 
Subjects who commenced ART prior to Week 48, but have not achieved HIV-1 RNA levels of 
< 50 copies/mL prior to Week 48 will also be followed until HIV suppression is achieved. 
4.2.4 
Long Term Follow-up 
All enrolled subjects will automatically transfer into long term follow-up. The long term follow-
up protocol is a separate protocol that provides assessments at defined intervals for the purposes 


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of determining possible long-term adverse events. The first long term follow-up visit is due 1.5 
years post-infusion and will continue at 6-monthly (± 1 month) intervals to 5 years post infusion 
and then annually thereafter to 15 years post-infusion. The specific procedures and 
requirements of long term follow-up are described in a separate protocol. 
All subjects will be informed of the long-term follow-up requirements at the time of consenting 
to this study. A separate and detailed consent form for long-term follow-up will be presented 
to all enrolled subjects at the time of completion of this study, or any time prior to the first 
scheduled long term follow-up visit. 
5. TRIAL POPULATION 
5.1 
General Considerations 
The minimum 6-week period off ART prior to Screening allows time to establish a “viral set 
point”. The historical, Screening 1, and Screening 2 CD4+ T lymphocyte count limits are 
determined to provide a safe limit for subjects to remain off ART for the complete pre- and 
post-infusion period. 
The DSMB will review data through Week 12 for the first 3 subjects in Cohorts 1 and 2 to 
decide upon on the busulfan dose for Cohorts 2 and 3, respectively. To facilitate timely 
recruitment, but allow adequate time for the DSMB decision, subjects for the next cohort can 
be identified and screening may commence after the third subject in the preceding cohort 
reaches the Week 12 post-infusion time point. Busulfan will not be administered until the 
DSMB recommendation is received. 
5.2 
Inclusion Criteria 
Eligible subjects will undergo screening assessments at two time points: Screening 1 to 
establish initial eligibility and Screening 2 to confirm eligible HIV RNA and CD4+ T 
lymphocyte levels, prior to the planned commencement of the first apheresis procedure. 
Potential subjects must satisfy all of the inclusion and exclusion criteria to be enrolled in the 
study and proceed with the CD4+ apheresis visit. 
In-A. Prior to any study-related procedures, signed informed consent indicating that they 
understand the purpose, risks and procedures required for the study and are willing to 
participate in the study 
In-B. Individuals aged 18 to 65 years of age (inclusive) at time of consent 
In-C. Documented HIV-1 infection ≥  6 months prior to Screening 1 
In-D. Previous treatment with antiretroviral agents that had a demonstrated suppressive effect 
(defined as plasma HIV RNA ≤ 50 copies/ml) 


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In-E.  A documented virologically-effective ART regimen option, as determined by the 
Investigator, taking into account prior ART experience and HIV geno/phenotyping 
analyses 
In-F. 
Not taking antiretroviral therapy for ≥  6 weeks prior to Screening 1, for one or more of 
the following reasons: 
 
i) Concerns over short-term or long-term toxicities associated with antiretroviral agents, 
or  
ii) Treatment fatigue from the daily regimen of life-long therapy 
In-G. Plasma HIV-1 viral RNA ≥ 5,000 copies/mL ± 0.2 log10 and ≤ 100,000 copies/ml ± 0.2 
log10 at Screening 1 and Screening 2 (i.e., ≥ 3,200 copies/mL and ≤ 160,000 copies/mL) 
In-H. CD4+ T lymphocyte count ≥  500 cells/µl (mm3) at Screening 1 and Screening 2 
5.3 
Exclusion Criteria 
Potential subjects will not be eligible if they meet any of the following criteria: 
Ex-A. Abnormal hematology at Screening 1: 
 
 
Absolute neutrophil count (ANC) < 1.5 x 103/µL 
 
 
Platelet count < 100 x 103/L  
 
Hemoglobin < 10 g/dL 
Ex-B. Abnormal biochemistry at Screening 1:  
 
Alanine aminotransferase (ALT) > 2.5 x ULN 
 
 
Total bilirubin > 1.5 x ULN  
 
Serum creatinine > 1.5 x ULN 
Ex-C. Detection of any CXCR4-tropic HIV-1 at Screening 1 
Ex-D. Evidence of co-infection with hepatitis B virus, hepatitis C virus, West Nile Virus, or 
HTLV-1 as detected at Screening 1 
Ex-E. Evidence of active TB infection determined by positive QuantiFERON®-TB 
Gold/IGRA test result and clinical confirmation at Screening 1 
Ex-F. ART or other antiretroviral therapy within 6 weeks of Screening 1 or any time during 
the pre-infusion period 
Ex-G. Documented history of CD4+ T lymphocyte count < 250 cells/µl (mm3) 
Ex-H. Any previous or current AIDS-defining illnesses (CDC Category C), including AIDS-
related dementia, with the exception of Kaposi's sarcoma confined to the skin 
Ex-I. History of malignancy or systemic chemotherapy within the last 5 years (i.e., subjects 
with prior malignancy must be disease-free for 5 years), except curatively-treated basal 


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cell carcinoma, cutaneous squamous cell carcinoma, or cervical or anal intra-epithelial 
neoplasia 
Ex-J. History of steroid-dependent asthma in the past 5 years 
Ex-K. History of seizure 
Ex-L. Any clinical history of hematologic diseases including leukemia, myelodysplasia, 
myeloproliferative 
disease, 
thromboembolic 
disease, 
sickle 
cell 
disorder, 
thrombocytopenia or leukopenia 
Ex-M. Class II-IV heart failure, according to the New York Heart Association classification 
Ex-N. Inadequate venous access for apheresis, as assessed prior to, or at Screening 1 
Ex-O. Current or planned systemic immunosuppressive or immunomodulatory medication 
Ex-P. Taking warfarin, aspirin, NSAIDS or any medication that is likely to affect platelet 
function or other aspects of blood coagulation, and unable to safely cease this 
medication during the periods of mobilisation/apheresis (19 days) and busulfan follow-
up (up to 6 weeks) 
Ex-Q. Participation in any study involving any investigational drug or medical device within 
30 days prior to Screening 1 
Ex-R. Receipt of a vaccine for HIV-1 or any gene transfer product at any time 
Ex-S. Prior treatment with recombinant G-CSF or busulfan or other stem-cell mobilizing or 
modulating agent within the previous 4 weeks 
Ex-T. Known hypersensitivity to busulfan, G-CSF (Neupogen™) or E. coli-derived proteins 
Ex-U. Subjects who will not accept transfusions of blood products 
Ex-V. Pregnant or breast-feeding at any time between Screening 1 and cell infusion (Day 0) 
Ex-W. History of alcohol or drug abuse within the 12 months prior to Screening 1 
Ex-X. Inability to understand and provide informed consent 
5.4 
Re-screening 
Non-qualifying Screening 1 test results that in the opinion of the investigator are not 
representative of the subject’s medical history or can possibly be attributed to a transient effect 
(for example, poor hydration on the day of the visit or short term mild infection) can be 
repeated, with the agreement of the Sponsor. 
A subject may withdraw or disqualify during the pre-infusion period and remain eligible to re-
screen only if, in the investigator’s opinion, the disqualifying result, though confirmed, was 
transient and not medically significant, and they have not commenced apheresis. In this event, 
the subject may repeat the screening process. The subject must sign a new consent form, be 


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assigned a new unique study ID and repeat all screening assessments to confirm they meet all 
eligibility criteria. 
5.5 
Provisions for Repeating Apheresis or Mobilization/Apheresis 
In the event that a subject has commenced apheresis or mobilization and study procedures 
cannot proceed for any reason (for example, acute infection/illness, change in personal 
circumstances, transduced cell product(s) that fail to meet release specifications, minimum 
HSPCtn dose not achieved, or failure of storage/transport conditions), the subject will have an 
option to repeat the applicable mobilization and/or apheresis procedures if within 14 weeks 
from Screening 1 and > 4 weeks between doses of G-CSF. 
Any manufacturing failure will be communicated to the site Investigator and Study Co-
ordinator, who will notify the subject. If the subject wishes to undergo a second round of 
apheresis or mobilization/apheresis, and the Investigator(s) agrees, the subject will be asked to 
provide consent using a supplemental information and consent specific to the required repeat 
procedures. 
Whether CD4+ apheresis alone and/or CD34+ mobilisation/apheresis are repeated will depend 
upon the nature of the process failure. The following considerations apply: 
- 
only the cellular product affected by the process failure will need to be repeated (i.e. if 
Ttn manufacturing was successful, only CD34+ mobilisation/apheresis will need to be 
repeated, and vice versa); 
- 
repeat CD34+ mobilisation should be scheduled at least four weeks from the date of the 
last G-CSF dose; 
- 
if repeat CD34+ mobilisation/apheresis only is required, the mobilisation regimen may 
be modified to include an extra dose of 0.24 mg/kg plerixafor on Day 3 of G-CSF, 
subject to MRC recommendation (refer to Sections 6.3.2); 
- 
the back-up rescue apheresis product of unmodified 1.2x106 CD34+ cells/kg will not be 
prepared if successfully prepared at the first attempt; 
Participants who do not return for repeat procedures will be discontinued and followed-up as 
described in Section 10 (Adverse event reporting). 
6. INVESTIGATIONAL AND CONCOMITANT TREATMENTS 
6.1 
Investigational Product 
The investigational product is defined as Cal-1 (LVsh5/C46) transduced CD34+ HSPC 
(HSPCtn) and Cal-1 (LVsh5/C46) transduced CD4+ T lymphocytes (Ttn). 
6.1.1 
Physical Description (preparation, handling, packaging, labeling & storage) 
The final Ttn and HSPCtn dosage forms will be labeled with the following information: 


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-
Name, address and telephone number of the manufacturer;  
-
Description of the content [Cal-1 transduced CD34+ HSPC (HSPCtn)] or [Cal-1 
transduced CD4+ T lymphocytes (Ttn)], dose (total cell number), volume, route of 
intended administration; 
-
The subject’s unique study identification number, initials and date of birth; 
-
Study reference code (CAL-USA-11);  
-
The phrase “For clinical trial use only” or similar wording; 
-
The required storage conditions; 
-
Date of manufacturing and Expiry date. 
The investigational products will be released with a Certificate of Analysis, which will include 
the results of release testing and other product identification criteria as determined by local 
regulations. Directions for handling and administration are provided in Appendix III.  
In addition, the back-up autologous CD34+ apheresis product containing 1.2x106 CD34+ 
cells/kg will be cryopreserved prior to the commencement of the HSPCtn manufacturing 
procedures. 
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Following the apheresis, the collected lymphocytes will be transferred to a dedicated 
processing facility. The cells will undergo an enrichment process to collect the CD4+ 
cell component, then will be transduced with Cal-1 and cultured for a total period of 14 
days. 
 
 
The final Ttn cellular product will be required to meet defined release criteria to proceed 
with infusion. 
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For each of the aphereses, the collected cells will be transferred to a dedicated 
processing facility.  Prior to any H[YLYR manipulations on the first CD34+ harvest, an 
aliquot of apheresis product containing 1.2x106 CD34+ cells/kg (of subject body 
weight) will be cryopreserved as a back-up (refer to Section 6.2). The remainder of this 
first CD34+ apheresis product will then undergo a positive selection process to collect 
the CD34+ component, then will be stored overnight, pooled with the purified CD34+ 
component from the second CD34+ harvest, before transduction with Cal-1 and culture 
for a total period of 3 days. 
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The final HSPCtn cellular product will be required to meet defined release criteria to 
and a minimum dose of 2.0x106 CD34+ cells/kg before proceeding with infusion (Day 
0). 
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All subjects will receive an autologous transplant of Cal-1 modified CD4+ (Ttn) and CD34+ 
(HSPCtn) cells. The dose will be dependent on the yields from the apheresis collections and 
laboratory purification, transduction and culture procedures for each individual subject. 
Recruitment to each cohort is sequential, with at least 3 subjects recruited consecutively to each 
cohort. 
In the event that either the Ttn or HSPCtn fails to meet the release criteria, or any other event 
occurs that prevents the successful preparation or release of either of these cellular products, 
infusion will not proceed. The subject will have an option to repeat the applicable apheresis or 
mobilization/apheresis procedure, subject to provision of informed consent (refer to Section 
5.5). 
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The following number of cells in the final Cal-1 modified infusion products are anticipated: 
-
Minimum 2.0x106 cryogenically preserved HSPCtn/kg of body weight with a 
transduction efficiency of  10% and  5 copies of the transgene per cell in an 
approximate volume of up to 50mL. 
-
0.5-20x109 total cryogenically preserved Ttn with a transduction efficiency of  10% 
and  5 copies of the transgene per cell in a maximum volume of 200mL. 
After pre-infusion assessments, the infusion products will be administered as rapid intravenous 
infusions in accordance with a standardized administration and handling directions (see 
Appendix III). To minimize cellular toxicity, re-infusion of the cryopreserved cells will occur 
immediately upon thawing. A minimum interval of 2 hours will be observed between 
administration of infusions of the modified cells to allow monitoring of vital signs and 
indications of any acute adverse reaction in the subject. The subject will continue to be 
monitored for 2 hours following the last infusion. 
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The following situations will be considered a product quality incident and will result in an 
investigation by the Sponsor’s Quality Assurance group to determine the root-cause and if any 
change to the laboratory or clinical procedures is warranted: 
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- 
Any occasion of inability to complete the manufacturing or release testing of a subject’s 
HSPCtn and/or Ttn cell product. 
- 
Failure to achieve required specifications for any release test of the HSPCtn and/or Ttn 
cell product. 
- 
An unexpected event detrimentally affecting either the cellular product or packaging 
that occurs despite observance of the standard operating procedures for preparation or 
release of the HSPCtn and/or Ttn cell product. 
- 
Any acute adverse event that the investigator suspects may have a causal relationship 
to the HSPCtn and/or Ttn cell product infused.  
A report will be issued to the investigator and the Sponsor with the results of the investigation 
and recommendations. The Sponsor has procedures and forms for the reporting, investigation 
and follow up of all incidents relating to product quality. 
6.2 
Back-up Apheresis Product 
Prior to any ex vivo manipulations on the first CD34+ harvest, an aliquot of unmanipulated 
apheresis product containing 1.2x106 CD34+ cells/kg (of subject body weight) will be 
cryopreserved. 
This back-up product is intended for autologous use only in the event that a subject experiences 
delayed hematopoietic recovery and/or bone marrow failure (as defined in Section 6.3.3). 
Hematopoietic recovery will be assessed at Week 12. If recovery is complete, the back-up 
apheresis product will be destroyed or released for research purposes, according to the subject’s 
consent. 
6.3 
Concomitant Medication and Therapies 
6.3.1 
G-CSF (Neupogen®) 
Subjects will receive G-CSF (Neupogen®; filgrastim) 10µg/kg QD by subcutaneous injection 
for 5 days, commencing 6 days after the first apheresis. The dose is to be calculated based on 
the subject’s weight as measured on the first day of G-CSF. Administration of the first G-CSF 
dose should be the final procedure of the visit, however the fourth and fifth dose must be 
administered on the morning prior to the CD34+ HSPC aphereses.  
The Day 4 G-CSF dose will be supplemented by a single dose of plerixafor (see Section 6.3.2 
below).The G-CSF dosing schedule should not be interrupted for reasons other than a total 
WBC  75,000 x 109/L, grade 3 or 4 musculoskeletal pain, headache or arthralgia unresponsive 
to analgesia, severe hypersensitivity reaction, other known rare serious side effects including 
splenic rupture, capillary leak syndrome or respiratory distress syndrome, or for any unexpected 
SAE that occurs during the G-CSF mobilization schedule, regardless of suspect cause. 


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In the case of a missed dose of G-CSF, apheresis may proceed if not more than 1 dose was 
missed out of the 5 day dosing schedule. 
All AEs and concomitant medication(s) and treatment dates and doses must be recorded.  
In the event of a subject repeating the mobilization, a minimum of 4 weeks must have elapsed 
since the previous final dose of G-CSF/apheresis. 
6.3.2 
Plerixafor (Mozobil®) 
Subjects will receive a single dose of plerixafor (Mozobil®) 0.24mg/kg (based on the same body 
weight used to calculate the G-CSF dose) by subcutaneous injection on Day 4 of G-CSF 
(Neupogen®) dosing. The dose is to be administered after completion of apheresis procedures 
on that day, and as late as possible to ensure a period of at least 9 hours, but preferably not more 
than 16 hours to the next (and final) scheduled CD34+ apheresis. 
All subjects receiving plerixafor should be observed for 30 minutes post-injection before 
discharge. Appropriate anti-emetics or anti-diarrhoeal medications should be prescribed by the 
Investigator as required to manage possible gastrointestinal symptoms. 
There is scope for increasing the total dose of plerixafor. In the event that the HSPCtn yield 
from any subject in this or any Calimmune clinical trial using the original aforementioned 
CD34+ mobilisation/apheresis regimen (i.e. 5 x 10µg/kg/day G-CSF, plus 1 x 0.24mg/kg 
plerixafor on Day 4, with 2 x 15L CD34+ aphereses) is < 2.0x106 HSPCtn/kg, a review of the 
mobilisation regimen will be undertaken by the study MRC. This review will consider an extra 
0.24mg/kg dose of plerixafor (based on the same body weight use to calculate the G-CSF dose) 
to be administered by subcutaneous injection on Day 3 of G-CSF dosing (as well as Day 4). 
All AEs and concomitant medication(s) and treatment dates and doses must be recorded. 
6.3.3 
Busulfan (Busulfex®) 
Busulfan is a potent cytotoxic drug and should be administered under the supervision of a 
qualified physician who is experienced in allogeneic HSPC transplantation and the use of 
cancer chemotherapeutic drugs. The dose is to be based on the subject’s weight as determined 
at the pre-busulfan assessment visit and the dose prepared, administered and monitored 
according to standardized directions (see Appendix IV). 
A single intravenous dose of Busulfex® will be administered to Cohort 2, while Cohort 3 will 
receive two doses of Busulfex® over 3 days (Day -4 and Day -2). Cohort 1 does not receive any 
Busulfex® conditioning.  
Busulfex® will be delivered as an intravenous infusion completing two days prior to the 
scheduled infusion of autologous HSPCtn and Ttn (Day 0). Busulfan conditioning will not 
proceed if the minimum HSPCtn dose of 2.0x106/kg is not achieved.  


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If, for any reason, the cell infusions cannot proceed as planned, busulfan conditioning should 
be postponed and rescheduled for as soon as possible. A delay of up to 2 weeks will not be 
considered a protocol deviation. 
Dosing for Cohort 2 will be a single 4mg/kg dose on Day -2. 
As recommended by the DSMB on June 24, 2015, dosing for Cohort 3 will commence at a total 
dose of approximately 6mg/kg and will be determined specifically based upon real-time, 
pharmacokinetic-guided dosing to achieve a 2-day total busulfan exposure of 8000 µMol/L•min 
area-under-the-curve (AUC). The first dose will be administered starting at 3mg/kg on Day -4, 
the second dose on Day -2. The second dose will be calculated based on subject-specific, real-
time pharmacokinetic results collected on Day -4 to achieve a target busulfan exposure of 8,000 
µMol/L•min AUC. The administration of busulfan using real-time, AUC-guided dosing 
provides additional safety measures for monitoring total busulfan exposure to a subject.  The 
target of 8,000 µMol/L•min AUC is recommended by the DSMB as a reduced intensity regimen 
based on the oncology population (the closest patient population to this study’s population). 
There is scope to reduce the dose within Cohort 3 if any subject experiences delayed 
hematopoietic recovery, as defined below. 
Delayed hematopoietic recovery is defined as an ANC < 0.5x103/µL (mm3) and/or platelet 
count of < 25x103/µL (mm3) after 42 days post-infusion. Bone marrow failure is defined as a 
protracted neutropenia (ANC < 0.5x103/µL (mm3)) and/or thrombocytopenia (platelets < 
25x103/µL (mm3)) after Week 12 post-infusion). 
The sponsor will notify the investigators in writing if delayed hematopoietic recovery occurs in 
any subject and if (in Cohort 3) the Busulfex® dose is to be reduced, or if bone marrow failure 
occurs and there is a temporary hold on administration of Busulfex® and subject enrolment 
pending DSMB safety assessment. 
All subjects will have had pre-emptive HLA genotyping and serotyping performed according 
to site standard-of-care protocol(s) at the pre-busulfan assessment visit as a precautionary 
diagnostic measure in case sustained bone marrow failure warrants consideration of allogeneic 
bone marrow transplantation. 
6.3.4 
Post-busulfan Infection Prophylaxis 
The following antimicrobial prophylaxis regimen will be administered to all subjects in Cohorts 
2 and 3 who receive busulfan: 
- 
Valacyclovir 500mg PO QD, commencing the same day as busulfan and continuing until 
Week 6 or until the ANC > 1x103/µL (mm3) on 2 consecutive visits. 
- 
Trimethoprim-sulfamethoxazole (TMP-SMX), 1 single strength tablet, PO QD 
(atovaquone 1500mg PO QD will be used for TMP-SMX allergic or intolerant subjects), 


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commencing if a subject’s CD4+ T cells are <200/ml until the CD4+ count has risen  > 
200 cells/ml on at least 2 occasions. 
- 
Fluconazole 200mg PO QD, commencing only if ANC < 0.5x103/µL (mm3), continuing 
until ANC > 1x103/µL (mm3) on 2 consecutive visits. 
6.3.5 
Antiretroviral Therapy 
Subjects will be recommended to re-commence ART if one or more of the following post-
infusion events occur: 
- 
CD4+ T lymphocyte counts decline below 350 cells/µl (mm3) confirmed by retest within 
14 days ±7 days; and/or 
- 
A decline in the CD4+ T lymphocyte percentage greater than 1/3 of the value at Pre-
busulfan Assessment visit, confirmed by retest within 14 days ±7 days; or 
- 
Plasma HIV RNA exceeds 250,000 copies/ml or > 20-fold increase from Pre-busulfan 
Assessment visit, whichever is less. Confirmed by retest within 1 month ± 7 days. Retest 
will be performed using the Abbott RealTime m2000 HIV-1 assay. For the purposes of 
comparative evaluation, all time points to the date the safety limit is observed, must be 
analyzed with the Abbott assay. Because of the possibility of cellular transduction with 
Cal-1 giving a falsely elevated result with the Roche assay, the decision to resume ART 
should be based on the Abbott assay confirmatory data (refer to Section 7.5 for details); 
or 
- 
Subject decision to re-commence ART regardless of pre-specified laboratory 
parameters; or 
- 
Pregnancy in a female subject. 
In this event, or any other clinical indication, the investigator or primary care physician is to 
advise recommencement of ART. The ART regimen that the subject commences should be as 
determined to be the most clinically appropriate for each individual, taking onto account their 
past history of compliance, tolerance and resistance as demonstrated through standard of care 
HIV-1 geno/phenotyping results. In the event of pregnancy, ART should be commenced in 
accordance with the current DHHS Guidelines (http://aidsinfo.nih.gov/guidelines). 
Subjects who commence ART will be discontinued from secondary analysis and follow up 
should continue as described in Section 8. 
6.3.6 
Other on-study concomitant medication and therapies 
Anti-platelet agents, anticoagulants or medications with known anticoagulant effects will not 
be allowed for at least 1 week prior to starting G-CSF, during G-CSF, and for at least 1 week 
after G-CSF dosing is completed (total period 19 days), and for the period starting with busulfan 


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administration until demonstrated hematopoietic recovery (an expected period of up to 6 
weeks). 
Subjects in Cohorts 2 and 3 should not be taking contraindicated medications for the periods of 
time as indicated in Appendix IV. 
In accordance with the eligibility criteria, subjects are not permitted use of systemic 
immunosuppressive/immunomodulatory therapy at study entry or at any time during the study 
period. Refer to Appendix II for the list of limited and prohibited immunosuppressive and 
immunomodulatory agents. If an adverse event necessitates this treatment, the subject will be 
discontinued and follow up should be performed as described in Section 8.  
Any diagnostic, therapeutic or surgical procedure performed during the trial period, should be 
recorded including the date, indication, description of the procedure(s), and any clinical 
findings. 
7. STUDY EVALUATIONS 
7.1 
Pre Infusion Phase 
7.1.1 
Consent 
Written, informed, consent of potential subjects may be obtained up to 3 months prior to a 
potential date for Screening 1. This is to allow evaluation of potential subjects through 
collection and review of general medical and HIV history, prior to formally commencing the 
screening process. 
7.1.2 
Pre-screening 
After provision of written, informed consent, potential subjects may undergo a pre-screening 
period, where data on the subject’s general health and HIV-related history can be obtained from 
past and/or current primary health care providers, and the potential subject’s suitability for 
screening evaluated. This pre-screening stage includes an optional provision to conduct 
laboratory tests to confirm the potential subject’s current HIV and co-infection status. These 
tests are routinely performed as part of standard clinical practice in the care of a HIV-infected 
individual (HIV RNA, lymphocyte phenotype, and/or hepatitis B and C). If the subject is 
suitable to proceed, all tests would be repeated at the Screening 1 visit. 
7.1.3 
Screening 1 
Within 3 months of written, informed consent, and preferably after completion of the optional 
pre-screening evaluations, potential subjects will undergo the screening procedures specified 
below. If Screening 1 cannot be scheduled within 3 calendar months of consent, the subject 
must be re-consented to proceed with Screening 1: 
- 
Demographics, including details of gender, date of birth, age, race. 


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- 
Documenting of medical and surgical history, including concurrent and recurrent 
illnesses (with detailed herpes simplex infection history), allergies (with detailed 
antibiotic allergy history), current and relevant recent past concomitant 
medications and therapies (including vaccinations). Collection of this information 
is anticipated to continue from consent throughout the screening period. Medical 
history review to confirm inclusion/exclusion criteria must be completed prior to 
commencement of the first (CD4+ T lymphocyte) apheresis procedure.  
- 
HIV history requires date of diagnosis, CD4+ T lymphocyte history and previous 
ART regimen(s) including the reason(s) for discontinuation. Subject self-reported 
history alone is not accepted as adequate documentation and independent medical 
records, such as laboratory reports, clinic or hospital progress notes and/or referral 
letters pre-dating consideration for this study must be available at the site as source 
documentation. Collection of this information is anticipated to continue through 
the screening period and must be completed prior to commencement of the first 
(CD4+ T lymphocyte) apheresis procedure. 
- 
Complete physical examination 
- 
Vital signs (temperature, blood pressure and pulse) 
- 
Chest x-ray 
- 
Assessment of venous access to ensure suitability to the apheresis procedures. This 
can be performed at any time between Consent and Screening 1 
- 
Clinical laboratory testing for the following: 
o Complete blood count with differential and platelet count 
o Biochemistry (fasting not required) 
o Pregnancy testing (serum β-HCG) for women of childbearing potential only 
o HIV-1 RNA in plasma 
o Lymphocyte phenotyping (CD3+/CD4+/CD8+) 
o HIV-1 R5/X4 tropism 
o Screening for co-infection with hepatitis B antibody and surface antigen, 
hepatitis C serology, West Nile virus RNA, tuberculosis QuantiFERON®-
TB Gold/IGRA, HTLV-1/2 serology, and syphilis serology 
7.1.4 
Screening 2  
Screening 2 is to be conducted at least 2 weeks after Screening 1. The following assessments 
will be performed at the second screening visit: 


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-
Assessment for new/changed adverse events 
-
Assessment for new/changed concomitant medications and therapies 
-
Clinical laboratory testing for the following: 
R Complete blood count with differential and platelet count 
R Biochemistry (fasting not required) 
R HIV-1 RNA in plasma 
R Lymphocyte phenotyping (CD3+/CD4+/CD8+) 
Medical and HIV-related history data can continue to be collected during this time to ensure 
qualification of eligibility criteria.
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Subject’s screening procedures must be complete and eligibility confirmed prior to proceeding 
to this apheresis visit. Recent CBC/differential with platelet count and serum electrolytes is 
required to optimize apheresis collection settings. If the Screening 2 study visit is performed  
2 weeks prior to this apheresis visit, the study site is responsible for ensuring these laboratory 
tests are performed within this timeframe. 
Subjects will attend the study center for visit assessments and apheresis to collect peripheral 
CD4+ T lymphocytes. Prior to apheresis, the following assessments will be performed: 
-
Vitals signs (temperature, blood pressure and pulse) 
-
Weight (shoes and outer clothing removed) 
-
Assessment for new/changed adverse events 
-
Assessment for new/changed concomitant medications & therapies 
-
Clinical laboratory testing for the following: 
R Complete blood count with differential and platelet count. 
R HIV-1 RNA in plasma 
R Lymphocyte phenotyping (CD3+/CD4+/CD8+) 
R Lymphocyte Development Studies 
The subject’s weight should be reported to the manufacturing laboratory to enable calculation 
of the anticipated Ttn dose. 
Subjects will undergo a 5L apheresis to collect an anticipated 2.5 to 5 x 108 total CD4+ T 
lymphocytes 
 
. An optimum target inflow rate and product volume collection rate 
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should be used to achieve maximal lymphocyte cell numbers. The apheresis volume may be 
adjusted during the study to yield the desired cell number. 
Apheresis product will be transported to a dedicated laboratory processing facility for 
purification, transduction and culture. Universal safety precautions will be followed at all times 
and personnel will be trained in applicable Good Manufacturing Practice (GMP) standards. 
If a repeat apheresis is required (in accordance with provisions described in Section 5.5), the 
same visit assessments and collection specifications will be followed. Any repeat apheresis visit 
must be confirmed with the Calimmune manufacturing laboratory 
7.1.6 
CD34+ Cell Mobilization 
G-CSF dosing begins exactly six days after the first (CD4+) apheresis, with no window period 
permitted. This 6 day interval between CD4+ T lymphocyte apheresis and the commencement 
of G-CSF is to allow the subject’s hematopoiesis to return to steady state before mobilization 
commences, and is precisely scheduled to accommodate the manufacturing timelines for both 
Ttn and HSPCtn products. The following assessments will be performed on the first day of G-
CSF, prior to administration of the first dose of G-CSF: 
- 
Targeted physical exam 
- 
Vitals signs (temperature, blood pressure and pulse) 
- 
Weight (shoes and outer clothing removed) 
- 
Assessment for new/changed adverse events 
- 
Assessment for new/changed concomitant medications & therapies 
- 
Urine pregnancy test (for women of childbearing potential only) 
- 
Clinical laboratory testing for the following: 
o Complete blood count with differential and platelet count 
o Biochemistry (fasting not required) 
o HIV-1 RNA in plasma 
o Lymphocyte phenotyping (CD3+/CD4+/CD8+). 
- 
Prescription and administration of first dose of G-CSF as the final procedure for 
this visit 
G-CSF administration is to continue on consecutive days for a total of 5 days as described in 
Section 6.3.1 and the Schedule of Events, with a single dose of 0.24mg/kg plerixafor (refer to 
Section 6.3.2), and CBC/differential measurement required on Day 4 of CD34+ mobilisation. 
Peripheral blood CD34+ enumeration will be performed on Days 3, 4 and 5. 


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In addition to administration of the daily dose of G-CSF, information on adverse events (AEs) 
and new or changed concomitant medications and therapies is to be collected and recorded 
daily.  
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Subjects will undergo two consecutive aphereses on Days 4 and 5 of the CD34+ mobilization 
to collect peripheral CD34+ HSPC. G-CSF doses are to be administered early on these days, 
prior to any other visit procedures or assessments. 
Prior to apheresis, the following assessments will be performed: 
-
Vitals signs (temperature, blood pressure and pulse) 
-
Weight (shoes and outer clothing removed) 
-
Assessment for new/changed adverse events 
-
Assessment for new/changed concomitant medications & therapies 
-
Clinical laboratory testing for the following: 
R Complete blood count with differential and platelet count 
R CD34+ enumeration (peripheral blood) 
Additionally, on the day of the final apheresis (Day 5), the following laboratory testing will 
also be performed on blood samples collected prior to commencement of the apheresis: 
R biochemistry and LFT panel (fasting not required); 
R plasma viral load. 
After completion of the first apheresis (Day 4), the subject will receive a dose of plerixafor, as 
described in Section 6.3.2. 
The subject’s weight should be reported to the manufacturing laboratory to enable calculation 
of the anticipated HSPCtn dose. 
 
 
 
Collection parameters are defined in Appendix V. An optimum target inflow rate and product 
volume collection rate should be used to achieve maximal cell numbers, yet minimise both red 
cell and platelet contamination, over a run time of 4 to 6 hours (approximately). 
The harvested apheresis product will be transported each day to a dedicated laboratory 
processing facility for purification, transduction and culture. Universal safety precautions will 
be followed at all times and personnel will be trained in applicable Good Manufacturing 
Practice (GMP) standards. 
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If a repeat CD34+ mobilization/apheresis is required (in accordance with provisions described 
in Section 5.5), the same mobilization schedule and specifications described in Section 7.1.6 
will be followed. Any repeat mobilization is to be scheduled at least 4 weeks after the last dose 
of G-CSF in the first attempt, and dates must be confirmed with the Calimmune manufacturing 
laboratory. 
7.1.8 
Administration of Busulfan- Cohorts 2 & 3 only 
Refer to Appendix IV for the busulfan preparation and administration procedures, including 
monitoring and PK data collection. 
Cohort 2 will receive a single dose 4mg/kg in the morning on Day -2. Cohort 3 will receive 4, 
3 or 2 mg/kg in the morning on both Day -4 and Day -2. The second dose will be calculated to 
achieve a target 8,000 µMol/L•min AUC, based on the pharmacokinetic data from the first dose. 
This visit can only proceed after confirmation has been received that the Ttn and HSPCtn 
products have met release testing criteria and the products are on site, and available for infusion. 
If, for any reason, the cell infusions cannot proceed as planned, busulfan conditioning should 
be postponed and rescheduled for as soon as possible.  
Subjects will attend a study visit up to 7 days prior to the planned commencement of busulfan 
in order to assess their general health, vital signs, and weight.  The required busulfan dose is to 
be prepared according to this weight. The following assessments are to be performed: 
- 
Targeted physical examination 
- 
Weight (shoes and outer clothing removed) 
- 
Vital signs (blood oxygen saturation to be monitored in addition to temperature, 
blood pressure and pulse) pre- and post-infusion 
- 
Assessment for new or changed adverse events 
- 
Assessment for new or changed concomitant medications & therapies 
- 
Urine pregnancy test (for women of childbearing potential only) 
- 
Clinical laboratory testing for the following: 
o Complete blood count with differential and platelet count 
o Biochemistry (fasting not required) 
o HIV-1 RNA in plasma 
o Lymphocyte phenotyping (CD3+/CD4+/CD8+) 
o Cal-1 marking/expression analysis – PB 
o Cal-1 marking/expression analysis – Subsets 
o Cal-1 integration site analysis 


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o Lymphocyte Development Studies 
o Specimen storage sample (plasma, serum and cryopreserved PBMC) 
Pre-emptive HLA genotyping and/or serotyping from peripheral blood samples will be 
collected at this visit according to the site’s internal standard-of-care protocol(s). 
Information on adverse events (AEs) and new or changed concomitant medications and 
therapies is to be collected and recorded. 
Females of child-bearing potential should have a urine pregnancy test performed prior to 
administration of busulfan. No other procedures are performed at this visit. 
7.1.9 
Cell Infusion (Day 0) 
The 5 week interval (± 1 week) between the final CD34+ HSPC apheresis and the day of 
infusion (Day 0) is to allow for the subject’s bone marrow to restore to steady state following 
the period of stimulation and for all manufacturing steps of transduction, culture, and release 
testing to be completed. The 7 day window period allows for flexibility to accommodate the 
subject’s and clinic schedules. 
The cryopreserved HSPCtn and Ttn products will be thawed after the pre-infusion clinical 
assessments are complete, immediately prior to planned infusion.  
The following pre-infusion assessments are to be performed: 
- 
Complete physical examination 
- 
Weight (shoes and outer clothing removed) 
- 
Vital signs (blood oxygen saturation to be monitored in addition to temperature, 
blood pressure and pulse) pre and post infusion 
- 
Assessment for new or changed adverse events 
- 
Assessment for new or changed concomitant medications & therapies 
- 
Urine pregnancy test (for women of childbearing potential only) 
- 
Clinical laboratory testing for the following: 
o Complete blood count with differential and platelet count 
o Biochemistry (fasting not required) 
o HIV-1 RNA in plasma 
o Lymphocyte phenotyping (CD3+/CD4+/CD8+) 
Following completion of pre-infusion assessments, each cell type will be thawed and 
administered as described in Appendix III. The cellular products will be administered 
consecutively as rapid intravenous infusions. The subject’s vital signs (temperature, blood 


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pressure, pulse, and oxygen saturation) will be monitored for 2 hours after each infusion for 
any acute adverse effects. The total process is anticipated to take between 4 to 5 hours. 
The infusion visit may be postponed only if busulfan conditioning has not been performed. 
Such a delay will not be considered a protocol deviation unless greater than 2 weeks. 
7.2 
Post Infusion Phase 
7.2.1 
Busulfan Follow-up 
Only for Cohort 2 and 3 subjects. 
Subjects will be asked to return to the clinic  every 3 days ± 1 day until Week 6 (or more 
frequently per PI discretion), and the following assessments performed: 
- 
Vital signs (temperature, blood pressure and pulse) 
- 
Assessment for new or changed adverse events 
- 
Assessment for new or changed concomitant medications & therapies 
- 
Local STAT complete blood count with differential and platelet count. Manual 
WBC/differential required. 
- 
A symptom-directed physical exam is to be performed in the event of any 
significant or grade 3 or 4 clinical or laboratory finding 
CBC/differential results must be reviewed prior to the subject leaving the clinic if a temperature 
of  100.5 F (38.0°C) is recorded. An ANC < 0.5x103/µL (mm3), with corresponding 
temperature of  100.5 F (38.0°C) is a medical emergency, and an investigator must be notified 
for immediate medical evaluation of the subject and admission (as soon as reasonably possible) 
to an accredited transplant facility (such as those with Foundation for the Accreditation of 
Cellular Therapy (FACT) accreditation). 
More frequent or extended follow up may be conducted if clinically indicated. 
7.2.2 
Weeks 1, 2, & 6 
The following assessments are to be performed: 
- 
Targeted physical examination 
- 
Vital signs (temperature, blood pressure and pulse). A local STAT CBC/differential 
must be ordered if temperature is  100.5°F (38.0°C), and the results reviewed 
prior to the subject leaving the clinic. An ANC < 0.5x103/µL (mm3), with 
corresponding temperature of  100.5°F (38.0°C) is a medical emergency, and an 
investigator must be notified for immediate medical evaluation of the subject and 
admission (as soon as reasonably possible) to an accredited transplant facility 


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(such as those with Foundation for the Accreditation of Cellular Therapy (FACT) 
accreditation). 
- 
Assessment for new or changed adverse events 
- 
Assessment for new or changed concomitant medications & therapies 
- 
Clinical laboratory testing for the following: 
o Complete blood count with differential and platelet count 
o Biochemistry (fasting or non-fasting) 
o HIV-1 RNA in plasma 
o Lymphocyte phenotyping (CD3+/CD4+/CD8+) 
o Cal-1 marking/expression analysis – PB 
7.2.3 
Week 4 
The following assessments are to be performed: 
- 
Targeted physical examination 
- 
Vitals signs (temperature, blood pressure and pulse). A local STAT CBC/differential 
must be ordered if temperature is  100.5°F (38.0°C) and the results reviewed prior 
to the subject leaving the clinic. An ANC < 0.5x103/µL (mm3), with corresponding 
temperature of  100.5°F (38.0°C) is a medical emergency, and an investigator 
must be notified for immediate medical evaluation of the subject and admission (as 
soon as reasonably possible) to an accredited transplant facility (such as those with 
Foundation for the Accreditation of Cellular Therapy (FACT) accreditation). 
- 
Weight (shoes and outer clothing removed) 
- 
Assessment for new or changed adverse events 
- 
Assessment for new or changed concomitant medications & therapies 
- 
Clinical laboratory testing for the following: 
o Complete blood count with differential and platelet count 
o Biochemistry (fasting not required) 
o HIV-1 RNA in plasma 
o Lymphocyte phenotyping (CD3+/CD4+/CD8+) 
o Cal-1 marking/expression analysis – PB 
o Cal-1 marking/expression analysis – Subsets 
o Specimen storage sample (plasma, serum and cryopreserved PBMC) 


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7.2.4 
Weeks 8, 16, 20, 28, 36 & 44 
The following assessments are to be performed: 
- 
Targeted physical examination 
- 
Vital signs (temperature, blood pressure and pulse). 
- 
Assessment for new or changed adverse events 
- 
Assessment for new or changed concomitant medications & therapies 
- 
Clinical laboratory testing for the following: 
o Complete blood count with differential and platelet count 
o Biochemistry (fasting or non-fasting) 
o HIV-1 RNA in plasma 
o Lymphocyte phenotyping (CD3+/CD4+/CD8+) 
7.2.5 
Weeks 12, 24 & 48 (End of Study) 
The following assessments are to be performed on Weeks 12, 24 and 48 (End of Study): 
- 
Complete physical examination 
- 
Vitals signs (temperature, blood pressure and pulse) 
- 
Weight (shoes and outer clothing removed) 
- 
Assessment for new or changed adverse events 
- 
Assessment for new or changed concomitant medications & therapies. 
- 
Clinical laboratory testing for the following: 
- 
Complete blood count with differential and platelet count 
- 
Biochemistry (fasting not required) 
- 
HIV-1 RNA in plasma 
- 
Lymphocyte phenotyping (CD3+/CD4+/CD8+) 
- 
Pregnancy testing (serum β-HCG) for women of childbearing potential 
- 
HIV-1 R5/X4 tropism 
- 
Cal-1 marking/expression analysis – PB 
- 
Cal-1 marking/expression analysis – Subsets 
- 
Cal-1 integration site analysis 
- 
Lymphocyte Development Studies 
- 
Specimen storage sample (plasma, serum and cryopreserved PBMC) 
- Bone marrow aspirate for Cal-1 marking/expression analysis 


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- Gut associated lymphoid tissue (GALT) biopsy for Cal-1 marking/expression 
analysis 
Bone marrow aspirate for Cal-1 marking/expression analysis must be performed within 1 week 
of the scheduled visit when all other clinical and laboratory assessments are performed. This 
procedure may also be performed as part of the Early Discontinuation/ Withdrawal visit if the 
subject discontinues or meets secondary analysis endpoint criteria). Two approximate 5ml pulls 
of the soft marrow drawn from the center of the hip bone will be performed. 
Gut associated lymphoid tissue (GALT) biopsy for Cal-1 marking/expression analysis must be 
performed within 1 week of the scheduled visit when all other clinical and laboratory 
assessments are performed. This procedure may also be performed as part of the Early 
Discontinuation/Withdrawal visit). 8 endoscopic biopsies will be collect from each of 2 sites 
within the sigmoid colon - at 10-15cm and 25-35cm from the anal verge of the sigmoid colon 
(i.e. 16 biopsies in total). 
If the subject discontinues or withdraws from the study within 8 weeks of the Week 12 or 24 
visits (i.e. having already recently undergone the scheduled bone marrow aspirate and GALT 
biopsies), additional bone marrow aspirate and GALT biopsies will be included as part of the 
Early Discontinuation/Withdrawal visit at the discretion of the Principal Investigator.  
7.2.6 
Weeks 32 & 40 
The following post-infusion assessments are to be performed: 
- 
Targeted physical examination 
- 
Vitals signs (temperature, blood pressure and pulse) 
- 
Assessment for new or changed adverse events 
- 
Assessment for new or changed concomitant medications & therapies 
- 
Clinical laboratory testing for the following: 
o Complete blood count with differential and platelet count 
o Biochemistry (fasting not required) 
o HIV-1 RNA in plasma 
o Lymphocyte phenotyping (CD3+/CD4+/CD8+) 
o Cal-1 marking/expression analysis – PB 
7.2.7 
Follow-up Extension 
The following assessments are to be performed in subjects who, at Week 48, remain off ART 
or have not achieved HIV RNA-1 levels of < 50 copies/mL if ART was previously commenced: 
- 
Targeted physical examination 


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- 
Vitals signs (temperature, blood pressure and pulse) 
- 
Assessment for new or changed adverse events 
- 
Assessment for new or changed concomitant medications & therapies 
- 
Clinical laboratory testing for the following: 
o Complete blood count with differential and platelet count 
o HIV-1 RNA in plasma 
o Lymphocyte phenotyping (CD3+/CD4+/CD8+) 
o Cal-1 marking/expression analysis – PB 
7.3 
Safety Evaluations 
The investigator must review laboratory reports, document this review and record any clinically 
relevant results or changes during the study as an adverse event. Where ever possible the 
attributed cause for the laboratory abnormality should be recorded as the AE term, not the 
abnormal result itself. Laboratory evaluations include: 
Complete Blood Count (CBC): Hemoglobin, hematocrit, red blood cell count, white blood cell 
count with differential and platelet count.  
Biochemistry: Bicarbonate, calcium, chloride, magnesium, potassium, and sodium electrolytes; 
glucose; urea; creatinine (including MDRD estimated creatinine clearance); creatine 
phosphokinase (CPK); and albumin, total, direct and indirect bilirubin, alkaline phosphatase, 
GGT, AST/SGOT and ALT/SGPT liver function tests. 
Fasting is not required, but status must be noted at the time of collection. 
Lymphocyte phenotype (T-cell count): Flow cytometry analysis of CD3, CD4 and CD8 cells 
reported as number of cells/µl (mm3) whole blood, percentage, and CD4:CD8 ratio. 
Pregnancy test (urine & serum): Serum β-HCG testing will be performed at the time points 
designated in the Schedule of Events for all women of child-bearing potential.  A urine 
pregnancy test must be performed on site, before any other study-related procedures are 
performed at commencement of mobilization, administration of busulfan and cell infusion. 
Additional urine pregnancy tests may be performed, as considered necessary by the investigator 
at any time during the study (for example, prior to busulfan, if it is to be administered). In the 
event of a positive urine pregnancy test, study procedures must be postponed (if possible) 
pending result of a confirmatory serum β-HCG test. A positive serum β-HCG test result will 
lead to screen-failure or discontinuation of the subject from the study. 
All confirmed pregnancies must be reported using the pregnancy reporting procedures 
described in section 10.2. 


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HIV-1 R5/X4 tropism: HIV-1 enters human cells in a process that comprises several steps, 
including the binding of the viral gp120 protein to the cellular receptor protein CD4 and a co-
receptor protein, usually one of the two chemokine receptors CCR5 (R5) and CXCR4 (X4). In 
addition to the purely X4- and R5-tropic viruses, there are also “dual-mixed” (D/M) strains, 
that are able to use both co-receptors. 
Sequencing and bioinformatics analysis will determine the HIV-1 tropism from HIV RNA in 
plasma samples. Enhanced sensitivity assays are capable of detecting as low as 0.3% of X4 
viral species. 
The test will be performed at various time points, as indicated in the Schedule of Events. 
Cal-1 integration analysis (‘insertional mutagenesis’): Integration site analyses will be 
performed by linear amplification–mediated PCR (LAM PCR) (Schmidt et al 2007) which is 
currently the most sensitive PCR-based method available to detect the presence or emergence 
of any predominant integration site(s). The test will be performed on DNA extracted from 
peripheral blood at various time points, as indicated in the Schedule of Events. A Cal-1 marking 
level of  1% in peripheral blood is required to determine if the LAM-PCR result can be 
interpreted as a true predominant integration site, therefore the assay will only be performed if 
Cal-1 marking is  1% at the corresponding time point. 
In the event that a predominant integration site(s) is detected, persistence will be confirmed by 
performing another analysis for clonality no more than 3 months later. A confirmed pattern of 
predominance will be further investigated to determine the nucleotide sequence adjacent to the 
site of vector integration, and this sequence compared to known sequences in the human 
genome database to identify if it is a known oncogene. 
Significance of oligo- or mono-clonality must be evaluated in association with clinical 
laboratory data (CBC/differential) and observations (physical exam) relevant to that point in 
time. A predominant integration site in the absence of any abnormal clinical observations is to 
be recorded as an AE and continue to be followed for clinical significance. In the event that a 
hematopoietic malignancy or other abnormality develops, the event is to be reported as an SAE. 
Refer to section 10 for more information on adverse event reporting. 
C46 immunogenicity studies: An immune response against the expressed C46 peptide is a 
theoretical risk, and testing for humoral and cell-mediated immune responses will be performed 
using ACD plasma and viably preserved PBMC aliquots from the stored specimens at pre-
infusion Week 12, Week 24 and Week 48 time points. Testing will be batched either by cohort 
or by time point and will be performed regardless of clinical presentation. Batch sizes and 
frequency will be tailored to minimize inter-assay variability, and optimal assay 
capacity/throughput. 


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Physical Exam (PE): Full PE will be performed at selected visits [Screening 1, Pre-busulfan 
Assessment, Week 12, Week 24, end of study (Week 48) or early discontinuation/withdrawal]. 
All other visits include a ‘targeted examination’ to include follow up examination of previously 
reported abnormalities and/or investigation of specific symptoms consistent with other clinical, 
laboratory or subject-reported observations. 
Pelvic/genitourinary, anal/rectal and detailed neurologic system examinations should be 
performed only if considered clinically required by the Investigator. 
Vital signs: Temperature, pulse and blood pressure will be obtained after the subject has been 
at rest for at least 5 minutes and prior to blood collection. Additionally, at the busulfan and cell 
infusion visits, pulse oximetry for oxygen saturation measurement will be measured (See 
Sections 7.1.8 and 7.1.9)  
Weight: Subject should be weighed wearing minimal clothing (i.e., outer coats or bulky items 
of clothing removed) and without shoes. Subjects should be asked to urinate before being 
weighed. 
Chest x-ray: Posterior-Anterior (PA) and lateral views 
Replication Competent Lentivirus (RCL): Tests for the presence of RCL will be performed by 
VSV-G PCR using subject peripheral blood DNA samples obtained pre-infusion and post-
infusion Weeks 12, 24 and 48. Samples of PBMC stored cryogenically or DNA extracted from 
peripheral blood may also be used to test for RCL at additional time points in the event of an 
adverse event that has suspect causality with Cal-1. These stored samples are collected at 
various time points as indicated in the Schedule of Events. 
If a positive VSV-G PCR signal is obtained, an additional peripheral blood DNA sample will 
be obtained as soon as possible for the purposes of confirming the result. A confirmed positive 
VSV-G signal will be reported as an SAE (per SAE reporting requirements in section 10.1.3) 
and blood collected for further investigation. 
7.4
Feasibility Evaluations 
Feasibility measures will include analysis of the Ttn and HSPCtn release and characterization 
criteria as defined in section 6.1. 
7.5
Efficacy Evaluations 
HIV-1 RNA: An FDA approved plasma HIV-1 RNA assay with a wide quantitative range will 
be used for real time monitoring of HIV-1 viral load monitoring. 
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Gene transfer using a lentiviral vector has been associated with a molecular cross-reaction with 
the COBAS® AmpliPrep/COBAS® TaqMan® HIV-1 RNA PCR assay 'H5DYLQHWDO 
and such cross-reactivity confirmed by Calimmune laboratory studies to also occur with Cal-1. 
For this reason, except for pre-screening, an EDTA plasma sample will be stored at each time 
point that a real time HIV-1 RNA analysis is performed. This stored sample will be used for 
batch analysis with the Abbott m2000 HIV-1 assay (quantitative range 40 to 10,000,000 
copies/mL). The Abbott assay does not show cross-reactivity with Cal-1. 
Batching will be by order of receipt unless otherwise indicated (according to safety limit 
retesting as described in Section 6.2.4). The Abbott m2000 assay will not be used to determine 
eligibility of subjects, and screen-failed subject samples will not be analyzed. 
Cal-1 marking/expression: will be analyzed by quantitative PCR for Cal-1 DNA (WPRE 
region) and RT-PCR for both C46 and sh5 RNA in the following cell types: 
-Peripheral blood (PB) 
-Peripheral blood subpopulations (Monocytes, granulocytes, CD4+ & CD8+ lymphocytes) 
-Bone marrow aspirate 
-Gut associated lymphoid tissue (GALT) 
Lymphocyte phenotype (standard T-cell count): Flow cytometry analysis of CD3, CD4 and 
CD8 cells will be reported as number of cells/μl (mm3) whole blood, percentage, and CD4:CD8 
ratio. 
Lymphocyte Development Studies - Thymopoiesis: Thymic function is known to decline with 
HIV-1 infection and disease progression. 
 
 
 
Lymphocyte Development Studies – Maturation: Flow cytometry analysis of 
 
 
 
 
 
  
 
 
 
 
Lymphocyte Development Studies - Inflammatory status: Flow cytometry analysis of the 
immune activation markers, 
 
 
 
 
 
 
 
 
 
 
 
 
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7.6
Exploratory Evaluations 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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7.7
Specimen storage 
Samples of cryopreserved PBMC, ACD plasma and SST serum will be frozen at various time 
points as indicated in the Schedule of Events. Additionally, any surplus DNA and/or RNA after 
Cal-1 marking/expression and integration analysis is completed, will also be stored. These 
samples will be archived for the duration of the study and the required long term follow up 
period. 
 
 
 
 
 
8. SUBJECT WITHDRAWAL/DISCONTINUATION 
Participants have the right to withdraw from the trial at any time for any reason without affecting 
their right to follow-up or standard of care treatment which they would otherwise receive. 
If a subject withdraws or discontinues from participation during the pre-infusion phase, no follow 
up will be performed other than for adverse events, as applicable. Adverse events that warrant 
discontinuation during this phase will be followed per standard of care and their outcome 
documented. SAEs will be followed as described in Section 10.1.3. 
If withdrawal or discontinuation was after the aphereses, but prior to busulfan administration, the 
transduction and culture processes will be completed for cells collected, and stored for a maximum 
period of 6 months. After this time, if it is confirmed that the subject will not proceed, the Ttn and 
HSPCtn cell products will be destroyed. 
Reasons a subject must withdraw during the pre-infusion phase include, but are not limited to: 
-
Serious adverse event relating to apheresis, mobilization or any other cause that prevents 
completion of the scheduled study procedures 
-
Adverse event that causes the subject to no longer be able to comply with the study 
requirements 
-
Death 
-
Pregnancy 
-
Subject request (withdrawal of consent)  
-
Protocol violation relating to eligibility 
-
Non-compliance with the G-CSF dosing schedule ( 2 doses missed) 
-
Any event that prevents the successful infusion of both Ttn and HSPCtn cellular products. 
-
Trial termination by the Sponsor 
Reasons a subject may withdraw during the post-infusion phase include, but are not limited to: 
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- 
Adverse event that causes the subject to no longer be able to comply with the study 
requirements 
- 
Pregnancy 
- 
Death 
- 
Subject request (withdrawal of consent) 
- 
Trial termination by the Sponsor 
If possible, subjects who meet any one of the post-infusion withdrawal criteria will be asked to 
attend an Early Discontinuation/Withdrawal visit and then continue safety follow up per the 
schedule of events until Week 48. In the event that a subject meets any of the secondary analysis 
endpoint criteria (discontinuation as defined in Section 9), they will be asked to attend an Early 
Discontinuation/Withdrawal visit and then continue per the schedule of events until Week 48 or 
until HIV suppression is demonstrated. If a discontinuation/secondary analysis endpoint is prior to 
Week 12, the bone marrow aspirate and GALT biopsies should be performed, if possible, as part 
of the Early Discontinuation/Withdrawal visit.  
The following assessments are to be performed as part of the Early Discontinuation/Withdrawal 
visit: 
- 
Complete physical examination 
- 
Vitals signs (temperature, blood pressure and pulse) 
- 
Weight (shoes and outer clothing removed) 
- 
Assessment for new or changed adverse events 
- 
Assessment for new or changed concomitant medications & therapies. 
- 
Clinical laboratory testing for the following: 
- 
Complete blood count with differential and platelet count 
- 
Biochemistry (fasting not required) 
- 
HIV-1 RNA in plasma 
- 
Lymphocyte phenotyping (CD3+/CD4+/CD8+) 
- 
Pregnancy testing (serum β-HCG) for women of childbearing potential 
- 
HIV-1 R5/X4 tropism 
- 
Cal-1 marking/expression analysis – PB 
- 
Cal-1 integration site analysis 
- 
Lymphocyte Development Studies 


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- 
Cal-1 marking/expression analysis – Subsets (conditions apply - see footnote 19 to 
Schedule of Events) 
- 
Specimen storage sample - plasma, serum and cryopreserved PBMC (conditions apply 
- see footnote 19 to Schedule of Events) 
As outlined in Section 7.2.5, an additional bone marrow aspirate and GALT biopsy may be 
performed at the discretion of the Principal Investigator and the consent of the subject if the subject 
discontinues or withdraws from the study within 8 weeks of the Week 12 or 24 visits (i.e. having 
already recently undergone the scheduled bone marrow aspirate and GALT biopsies). 
For the purposes of data analysis, the date and reason for discontinuation or secondary analysis 
endpoint criteria will be captured in the source documentation and CRF. 
In the event that a subject decides to withdraw consent, a reason does not have to be provided. 
However, every attempt should be made to counsel the subject on the implication to the study and 
their ongoing safety monitoring if they choose to withdraw. He/she should be asked to attend long 
term follow up. The outcome of such discussions should be documented. 
A subject will be considered lost to follow-up if contact cannot be resumed after reasonable and 
documented attempts by the investigator. A minimum of 3 attempts are required over a reasonable 
time frame, with both the subject directly and the alternate contacts provided at study entry. At 
least 1 attempt must be in writing before a subject can be declared lost to follow up. Should a 
subject re-initiate contact after being declared lost to follow up, the subject can be re-instated and 
re-commence safety follow up visits at the next scheduled time point. 
Participants who withdraw or discontinue early from the trial after infusion (Day 0) will not be 
replaced. An excessive rate of withdrawals/discontinuations can render the trial non-interpretable; 
therefore, every care should be taken by the investigator during the subject selection and consenting 
process to ensure suitable subjects are selected. 
9. STATISTICAL METHODS 
This is a Phase I/II study, and the sample size has not been based on formal power considerations. 
No recruitment limit is set for any of the participating sites, with the only restriction being 
consecutive enrollment that does not exceed 4 subjects per cohort. Subjects for the next cohort will 
not be treated (i.e. commence busulfan) until the DSMB recommendations are received. 
Safety 
In terms of safety data, pooling all subjects across the three arms, the study will have at least an 
80% probability of observing one or more serious adverse events if the true rate of these events in 
a subject is 12.6% or higher for 12 subjects, or ≥ 16.4% if 9 or more subjects. Pooling the busulfan 
subjects will give at least an 80% probability of observing one or more serious adverse events that 
occur with a true rate of 18.2% per subject for n=8, and 23.5% for n=6. Within any arm of four 


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subjects, the study will have 80% probability of detecting events with a true rate of 33.1% per 
subject. 
Hence the study will be well powered to detect only serious adverse events that occur with a 
reasonably high probability. The study will not be well powered to detect events that are rarer than 
about 10-20% per subject. 
)HDVLELOLW\ 
Feasibility measures will include analysis of the Ttn and HSPCtn release criteria and 
characterization. Correlations between safety and secondary efficacy data with feasibility measures 
will be exploratory and made where a causal relationship of an adverse event to the investigational 
product or study procedure is classified as possible, probable or very likely. It is accepted that these 
analyses will have limited power. 
.H\HIILFDF\YDULDEOHV 
Pooling all subjects, and assuming that the within subject variability corresponds to a standard 
deviation of 1.0 logs, the study will have 80% power to detect a mean change in Log10 HIV-1 RNA 
of 0.81 logs (2-alpha = 5%) for 12 subjects, , or  0.94 logs if 9 or more subjects. For changes in 
CD4+ T lymphocyte count across all subjects, assuming the within subject variability corresponds 
to a standard deviation of 250 cells/μL (mm3) (Australian HIV Observational Database – data on 
file), the study will have 80% power to detect a mean change in CD4+ T lymphocyte count of 205 
cells/μL (mm3) for 12 subjects, or  235 cells//μL (mm3) if 9 or more subjects. 
 
 
 
6HFRQGDU\DQDO\VLVHQGSRLQWV 
Early endpoints for secondary analysis (discontinuation) include: 
-
Commencement of ART for any reason 
-
Commencement of systemic immunosuppressive therapy/immunomodulatory therapy. 
Refer to Appendix II for the list of limited and prohibited immunosuppressive and 
immunomodulatory agents. 
9.1
Statistical Analyses 
The primary analysis will be conducted when all recruited subjects have completed 48 weeks 
follow-up or have ceased trial follow-up before that time.  
Primary analyses will include all subjects who received both cell infusions. Subjects who 
consented to the trial, but subsequently were not infused with the investigational product, will 
be excluded. If any subjects have partial or incomplete infusions, then sensitivity analyses will 
also be performed excluding these subjects. 
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Subject baseline demographic and clinical information will be summarized by treatment 
received and overall. There will be no formal comparison of the treatment groups in terms of 
baseline factors (i.e. no S-values). 
Treatment received will be summarized, as will duration of subject follow-up. Any subjects 
discontinuing (i.e. starting antiretroviral or prohibited concomitant medication treatment), 
withdrawing (e.g. withdrawing consent to trial follow-up, lost to trial follow-up etc.) will be 
listed. The time to starting antiretroviral treatment will be summarized using Kaplan-Meier 
plots. 
6DIHW\ 
The severity of clinical adverse events and laboratory safety parameter adverse events will be 
graded according to DAIDS criteria. The original term used in the case report form (CRF) to 
document adverse events will be coded using the current Medical Dictionary for Regulatory 
Activities (MedDRA). 
Numbers of individual adverse events, in numbers of subjects, will be summarized by severity 
and treatment, both overall and by nominal study week. Adverse events will also be 
summarized and aggregated by body system for clinical events. 
The worst severity of each clinical and laboratory adverse event, for each subject, will be 
summarized by treatment. 
All grade 3 and 4 adverse events, and any other events that lead to a subject ceasing trial follow-
up, will be listed by treatment, with duration and resolution. 
)HDVLELOLW\
Feasibility measures such as the number of Ttn and HSPCtn manufacturing procedures 
successfully completed (i.e. complying with all release criteria); number of gene modified cells, 
as affected by CD4+ and CD34+ purity, transduction efficiency, and viability; and the number 
of target cells harvested will be summarized overall.  
 
 

 
 

 
 

 
 
 
Associations with continuous safety and secondary efficacy data, such as laboratory parameters, 
will use repeated measures regression analyses. Associations with binary events will compare 
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the feasibility measures in those patients with and without events using linear regression 
methods or non-parametric equivalents as appropriate. 
(IILFDF\HQGSRLQWV 
Log10 HIV-1 RNA, lymphocytes (CD4+ T lymphocyte count, CD4+ %, CD4:CD8 ratio), 
measures of Cal-1 marking/expression and lymphocyte development will be plotted over time 
for each individual subject during the period(s) of time they remain off ART, and will be 
summarized for each nominal study week by treatment and overall. Batch analysis data from 
the Abbott RealTiPe m2000 assay will be used for these analysis. 
Changes in Log10 HIV-1 RNA and CD4+ T lymphocyte count from baseline will be formally 
compared in all subjects using one-sample t-tests or non-parametric equivalents as appropriate. 
 
 
 
 
 
9.2
Preliminary Analyses 
There are two planned safety analyses and one preliminary analysis.  
The first safety analysis will be when three subjects in Cohort 1 (all receiving Ttn and HSPCtn 
with no busulfan) have completed 12 weeks follow-up. The second safety analysis will be timed 
for when three subjects in Cohort 2 (all receiving Ttn and HSPCtn with single dose of busulfan) 
have completed 12 weeks follow-up. The independent DSMB will conduct a complete review 
of safety data at each of these analyses before administration of study treatment in the following 
cohort of subjects is commenced. 
At each safety analysis, all subjects’ safety data will be summarized including all available data 
up to the time the analysis is conducted. Measures of Cal-1 marking/expression will also be 
summarized. There will be no formal statistical stopping rules; rather the study will continue 
on the basis that the medical review Committee determines that there is no evidence of safety 
concerns to necessitate study cessation. Reasons for not continuing with the next planned cohort 
may include the occurrence of grade 4 elevation of transaminases (>10.0 x ULN ALT and AST) 
or thrombocytopenia (<25,000/mm3 or 25x109/L), unanticipated incidence, severity or 
frequency of AE/SAEs, and outcome of Ttn/HSPCtn manufacturing processes. Efficacy 
indicators, such as the degree of Cal-1 marking in peripheral blood, GALT and bone marrow 
will also be assessed. 
The preliminary analysis will include safety data and secondary endpoints when all subjects 
have completed 24 weeks follow-up. 
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10. ADVERSE EVENT REPORTING 
Timely, accurate, and complete reporting and analysis of safety information is crucial for the 
protection of subjects, investigators, and the Sponsor, and are mandated by regulatory agencies 
worldwide. The Sponsor or its contracted designee(s) has established Standard Operating 
Procedures (SOPs) in conformity with applicable regulatory requirements to ensure appropriate 
reporting of safety information. 
10.1 
Adverse Event Definitions and Criteria 
An adverse event (AE) is any untoward medical occurrence in a clinical study subject 
administered a medicinal (investigational or non-investigational) product. An AE does not 
necessarily have a causal relationship with the treatment. An adverse event can therefore be any 
unfavorable and unintended sign (including an abnormal finding), symptom, or disease 
temporally associated with the use of a medicinal (investigational or non-investigational) 
product, whether or not related to that medicinal (investigational or non-investigational) 
product (Definition per International Conference on Harmonization [ICH]). For the purposes 
of this study, this definition also includes the study specified procedures. 
An AE also includes any occurrence that is new in onset or aggravated in severity or frequency 
from the baseline condition, or abnormal results of diagnostic procedures, including laboratory 
test abnormalities. 
AE reporting starts on the day of the Screening 1 visit (with the first study-related procedure) 
and ends at study completion. In the event of withdrawal of consent, the subject will be asked 
to continue in long term follow up to allow ongoing collection of AE and safety information. 
All AEs, regardless of seriousness, severity, or presumed relationship to the investigational 
product or study procedures, must be recorded using medical terminology in the source 
document and the CRF. Whenever possible, diagnoses may be recorded when signs and 
symptoms are due to a common etiology (e.g., cough, runny nose, sneezing, sore throat, and 
head congestion should be reported as “upper respiratory infection”). Investigators must record 
their opinion concerning the relationship of adverse events to study therapy or procedures in 
the source document. All measures required for adverse event management must be recorded 
in the source document. 
Analysis for emergence of any predominant site of integration of Cal-1 in peripheral blood is 
routinely conducted throughout the post-infusion study period (as per the schedule of events). 
Clonal expansion of any cell with a particular integration site could be an early indication of 
malignancy secondary to the insertion of Cal-1. In the event that a predominant integration 
site(s) is detected, clinical significance must be evaluated in association with laboratory data 
(CBC/differential) and observations (physical exam) relevant to that point in time. A 
predominant integration site in the absence of any abnormal clinical observations is to be 
recorded as an AE and continue to be followed for clinical significance. In the event that a 


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hematopoietic malignancy or other abnormality develops, the event is to be reported as an SAE 
(see section 10.1.4). 
10.1.1 Adverse Event Severity Criteria 
Adverse events are to be graded into 4 potential severities: mild, moderate, severe or potentially 
life threatening, according to the Division of AIDS Table for Grading the Severity of Adult 
Adverse Events (see Appendix I). If the need arises to grade a specific clinical or laboratory 
adverse event that is not identified in the DAIDS AAE grading table, the “Estimating Severity 
Grade” is to apply.  
If the severity of an adverse event could fall under either one of two grades (e.g., the severity 
could be either grade 1 or grade 2), select the higher of the two grades. 
10.1.2 Adverse Event Causality/Association 
An adverse event is considered associated with the use of the investigational product, 
concomitant medication or study procedure if the attribution is possible, probable, or very likely 
by the definitions below: 
Not related: An adverse event that is not considered to be associated or attributed to the use of 
the investigational product or procedure. 
Doubtful: An adverse event for which an alternative explanation is more likely, e.g., 
concomitant drug(s), concomitant disease(s), or the relationship in time suggests that a causal 
relationship is unlikely. 
Possible: An adverse event that might be due to the use of the investigational product or 
procedure. An alternative explanation, e.g., concomitant drug(s), concomitant disease(s), is 
inconclusive. The relationship in time is reasonable; therefore, the causal relationship cannot 
be excluded. 
Probable: An adverse event that might be due to the use of the investigational product or 
procedure. The relationship in time is suggestive. An alternative explanation is less likely, e.g., 
concomitant drug(s), concomitant disease(s). 
Very likely: An adverse event that is listed as a possible adverse reaction in the applicable 
product reference safety information and cannot be reasonably explained by an alternative 
explanation, e.g., concomitant drug(s), concomitant disease(s). The relationship in time is very 
suggestive. 
For the investigational product, the expectedness of an adverse event will be determined by 
whether or not it is described in the Investigator's Brochure. For the protocol required marketed 
products such as G-CSF (Neupogen®), plerixafor (Mozobil®) and busulfan (Busulfex®), the 
expectedness of an adverse event will be determined by whether or not it is listed in the 
approved label for the product. For study required procedures, the expectedness of an adverse 


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event will be determined by known risks as described in the subject information and consent 
form and according to the investigator’s judgment. 
10.1.3 Serious Adverse Event 
A serious adverse event (SAE) as defined by ICH/GCP is any untoward medical occurrence 
that at any dose meets any of the following conditions: 
- 
Results in death 
- 
Is life-threatening (the subject was at risk of death at the time of the event. It does 
not refer to an event that hypothetically might have caused death if it were more 
severe or if left untreated) 
- 
Requires inpatient hospitalization or prolongation of existing hospitalization 
- 
Results in persistent or significant disability/incapacity, or 
- 
Is a congenital anomaly/birth defect 
Medical and scientific judgment should be exercised in deciding whether it would be 
appropriate to report an event that does not meet the above criteria, but may be an important 
medical event. These situations should also be considered as serious and be reported as an SAE. 
For gene transfer studies, additional events to be reported as SAEs include, but are not limited 
to: 
- 
Any malignancy, with the exception of basal cell carcinoma, squamous cell 
carcinoma or carcinoma of the cervix in situ 
- 
A predominant integration site as detected by the Cal-1 integration assessment assay 
in association with abnormalities in clinical laboratory data or physical examination 
- 
A confirmed positive VSV-G PCR signal for detection of Replication Competent 
Lentivirus. 
All SAEs occurring during this study must be reported by the investigational staff to the 
appropriate Sponsor contact person within 24 hours of their knowledge of the event. Contact 
details for SAE reporting are provided on the contacts page of this protocol. The appropriate 
SAE reporting form template must be used. 
SAEs that have not resolved by the end of the study, or that have not resolved upon 
discontinuation of the subject’s participation in the study, must be followed until any of the 
following occurs: 
- 
The event resolves 
- 
The event stabilizes 
- 
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- 
The event can be attributed to agents other than the study drug or to factors unrelated 
to study conduct 
- 
It becomes unlikely that any additional information can be obtained (subject or 
healthcare practitioner refusal to provide additional information, lost to follow-up 
after demonstration of due diligence with follow-up efforts) 
Any event requiring hospitalization that occurs during the course of a subject’s participation in 
this clinical study must be reported as a serious adverse event, except hospitalizations for the 
following reasons: 
- 
Social reasons in absence of an adverse event 
- 
Admissions that do not require an overnight stay (for example, admission for a day 
procedure or for observation for less than a 24 hour period). 
- 
Planned surgery or procedure before entry into the study (must be documented in 
the source document and CRF) 
In the event of a subject death secondary to any malignancy, or to any hematopoietic, 
immunologic or neurologic abnormality, the investigator must follow up to try to obtain post 
mortem tissue samples for the purposes of analysis for Cal-1. Subjects will be informed of this 
requirement and asked to consider their wishes in this regard. A subject is not obliged to agree 
to autopsy in order to participate in the study and consent for autopsy will be documented 
separately. Tissue samples to be requested include: 
- 
Any malignant or benign tumor 
- 
Bone marrow 
- 
Lymph node 
All tissue samples obtained will be processed to extract DNA for the purposes of PCR analysis 
for Cal-1 marking, integration analysis and RCL. 
10.1.4 Serious & Unexpected Suspected Adverse Reaction (SUSAR) 
An unexpected serious suspected adverse reaction is one for which the nature or severity is not 
consistent with the applicable reference safety information, and thus requires expedited 
reporting to authorities and all participating investigators as required according to local 
guidelines and regulations. Medical and scientific judgment should however be exercised in 
deciding whether expedited reporting is also appropriate in situations other than those listed 
above. For example, important medical events may not be immediately life-threatening or result 
in death or hospitalization but may jeopardize the subject, may require intervention to prevent 
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In the event of a SUSAR, storage samples from the subject may undergo analysis for RCL, 
integration analysis and marking/expression testing. Additional blood and/or tissue samples 
may be requested to enable further evaluation. 
SUSARs that represent a serious threat to public health will be reported within 48 hours. Fatal 
and life threatening SUSARs will be reported as soon as possible, and not later than 7 calendar 
days from the date the event report was initially received from the reporting investigator. All 
other SUSARs and safety issues warranting expedited reporting will be reported no later than 
15 calendar days from the date the event report was initially received from the reporting 
investigator. In each case, relevant follow up and outcome information will be sought and 
submitted as soon as possible. The Sponsor (or contracted designee) assumes responsibility for 
appropriate reporting of adverse events to the regulatory authorities. The Sponsor will also 
report all SUSARs to the investigator. The investigator (or Sponsor where required) must report 
these events to the appropriate Institutional Ethics Committee (IEC) and Institutional Biosafety 
Committee (IBC) that approved the protocol unless otherwise required and documented by the 
IEC and IBC. 
10.2 
Notification of pregnancy 
Female subjects of child-bearing potential, as well as male subjects with partners of child-
bearing potential must practice an acceptable method of effective birth control while in the 
study. Pregnancy occurring in either a female study subject or the partner of a male subject in 
the trial must be reported to the Sponsor by the investigational staff within 24 hours of their 
knowledge of the event using the appropriate pregnancy notification form. The study subject 
and/or female partner should be counseled, and the risks of continuing the pregnancy discussed, 
as well as the possible effects on the fetus. 
Any study subject who becomes pregnant during the study will be discontinued from secondary 
analysis, but asked to continue in follow up to allow collection of adverse event and pregnancy 
outcome information. If pregnancy occurs prior to Week 12, the scheduled bone marrow 
aspirate and GALT biopsy procedures will not be performed. The investigator is to assess if a 
pregnant subject should continue with the scheduled blood collections. This assessment is to be 
documented in the subject’s medical record/clinical source document. 
Follow-up information regarding any postnatal sequelae in the infant will be required. 
Abnormal pregnancy outcomes are considered SAEs and must be reported using the SAE 
notification form. 
Contact details for notification of pregnancy are provided on the contact information page of 
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11.SPECIAL CONSIDERATIONS 
11.1
Study-Specific Design Considerations 
The safety profile of Cal-1 has not been established, subjects may therefore be placing 
themselves at risk of unexpected acute, sub-acute and/or long term adverse events by 
participating in this study. 
To participate in this study, potential subjects must have made a prior decision to cease ART 
due to concerns over short-term or long-term toxicities associated with antiretroviral agents, or 
treatment fatigue from the daily regimen of life-long therapy. Efficacy of Cal-1 has not been 
established and subjects could fail to achieve optimal virologic control during the course of the 
study. To mitigate potential risk to the subject, only subjects with a documented virologically-
effective ART regimen option will be enrolled and HIV-related criteria for the commencement 
of ART are specified in Section 6.2.4. 
The potential risks that are apparent in the present study include: 
-
exposure to the investigational agent, with the potential for unknown acute, sub-acute 
and/or long term side effects; 
-
exposure to the alkylating bone morrow conditioning agent busulfan (Busulfex®) with 
the potential for both known and unknown side effects, including potential 
carcinogenicity; 
-
possibility of mishap during the cell processing procedures, resulting in inability to 
proceed with infusion of the modified cell product; and 
-
the inherent risks associated with venipuncture, apheresis and biopsies. 
The study has been designed to balance these risks with potential benefit and improved 
understanding of Cal-1 and the associated procedures. 
The use of the 3 cohorts in this study does not represent an ethical compromise because all 
subjects will receive the same post-infusion follow up and this study is designed to answer 
important questions about Cal-1, including the benefit/risk of using busulfan as a means to 
increasing bone marrow engraftment of the transduced HSPCtn population as well as provide 
scientific guidance on using Cal-1 in an ART-intolerant subject population. 
11.2
Ethical and Regulatory Information 
This study is being conducted under an IND (
) and has undergone public 
review by the Recombinant DNA Advisory Committee of the NIH Office of Biotechnology 
Activities. The study is registered and listed in clinicaltrials.gov (NCT01734850). 
Before the start of the study, the investigator (or Sponsor where required) will provide the 
Institutional Ethics Committee (IEC) and Institutional Biosafety Committee (IBC) with current 
and complete copies of the following documents: 
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Final protocol and, if applicable, amendments 
- 
Sponsor-approved informed consent form (and any other written materials to be 
provided to the subjects, including any Sponsor-approved recruiting materials) 
- 
Investigator’s Brochure and, if applicable, amendments 
- 
Any other documents that the IEC or IBC requests to fulfill its obligation 
This study will be undertaken only after the IEC and IBC has given full approval of the 
submitted material, and the Sponsor has received a copy of this approval. 
During the study, the investigator (or Sponsor where required) will send the following 
documents and updates to the IEC and IBC for their review and approval, where appropriate: 
- 
Protocol amendments 
- 
Revision(s) to informed consent form and any other written materials to be provided to 
subjects 
- 
If applicable, new or revised subject recruiting materials approved by the Sponsor 
- 
Investigator’s Brochure amendments or new edition(s) 
- 
Summaries of the status of the study at intervals stipulated in guidelines of the IEC and 
IBC (at least annually) 
- 
Reports of adverse events that are serious, unlisted, and associated with the 
investigational drug 
- 
New information that may adversely affect the safety of the subjects or the conduct of 
the study or represent a serious threat to public health 
- 
Deviations from, or changes to, the protocol 
- 
Notification if a new investigator is responsible for the study at the site 
- 
Annual Safety Report and Line Listings, where applicable 
- 
Recommendations of the independent Data safety Monitoring Board 
- 
Any other requirements of the IEC and/or IBC 
For all protocol amendments (excluding the ones that are purely administrative, with no 
consequences for subjects, data or trial conduct), the amendment and applicable informed 
consent form revisions must be submitted promptly to the IEC and IBC for review. Approval 
must be obtained in writing before implementation of the change(s). 
If any study subject incurs an injury or health problem that is due to Cal-1 or participation in 
this study, the Sponsor will cover the costs of investigations and necessary treatment. 


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Regulatory agencies may be asked to adjudicate the likelihood of attribution to causality to Cal-
1. 
At the end of the study, the investigator (or Sponsor where required) will notify the IEC and 
IBC about the study completion. 
Long term follow up is a requirement for all recipient of experimental gene transfer therapy and 
is an important means of determining long term ethical and medical implications. All subjects 
enrolled in a Cal-1 protocol will be informed of the long term follow up requirements at the 
time of initial consent. 
11.3 
Informed Consent 
Informed consent is a process and the subject will be given sufficient time to read the informed 
consent form and the opportunity to ask questions and consider the answers. Before enrollment 
in the study, the investigator or an authorized and qualified member of the investigational staff 
must explain to potential subjects the aims, methods, reasonably anticipated benefits, and 
potential hazards or discomforts of the study, and the obligations that participation in the study 
and long term follow up may entail. This process of consent should be documented in the source 
document and completion of the process documented by means of each subject personally 
dating their own signature on the study consent form. The consent form must be signed before 
any study-related procedure is performed, and may be signed up to 3 months prior to the 
Screening 1 study visit. The consent form that is used must have prior written approval by the 
reviewing IEC. The informed consent should be in accordance with principles that originated 
in the Declaration of Helsinki, current ICH and GCP guidelines, applicable regulatory 
requirements, and Sponsor policy. 
Potential study subjects will be told that alternative treatments are available if they refuse to 
take part and that such refusal will not prejudice future treatment. They will be informed that 
choosing not to participate will not affect the care the subject would otherwise receive for the 
treatment of his or her HIV infection. 
Potential study subjects will be informed that their participation is voluntary and that they may 
withdraw consent to participate at any time. If they choose to withdraw, subjects will be asked 
to continue in follow up to enable ongoing monitoring of their health for any long term effects 
of the investigational treatment and contribution to safety data. This includes follow up to at 
least Week 48 and the separate long term follow up study. 
All subjects will be asked to nominate a minimum of one alternative contact to help ensure 
contact is maintained with the subject throughout the study and the long term follow up period. 
By signing the informed consent form, the subject is authorizing such access, and agrees to 
allow a member of the site study staff to contact the subject and/or their nominated contact(s) 
for the purpose of the study and for follow up for at least 15 years post infusion. 


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After having obtained written consent, a copy of the signed informed consent form must be 
given to the subject. 
If the subject is unable to read or write, an impartial witness should be present for the entire 
informed consent process (which includes reading and explaining all written information) and 
should personally date and sign the informed consent form after the oral consent of the subject 
is obtained. 
Finally, potential study subjects will be told that the investigator will maintain a subject 
identification register for the purposes of long-term follow-up and that their records may be 
accessed by health authorities and authorized Sponsor staff without violating the confidentiality 
of the subject, to the extent permitted by the applicable law(s) or regulations. 
11.4 
Long Term Follow-up 
Current requirements are for all gene transfer recipients to be followed for 15 years post 
administration of the gene transfer agent to allow safety monitoring and evaluation of recipients 
for potential long term associated adverse events. 
As part of the Cal-1 program, all clinical trial subjects will roll over into a separate long term 
follow up protocol. This enables completion of the immediate objectives of the clinical trial and 
provides a streamlined process for all subjects to enter into an established long term follow up 
protocol. Long term follow up will commence 1.5 years post infusion (Day 0) and will continue 
at 6-monthly (± 1 month) intervals to 5 years post infusion and then annually thereafter. 
The long term follow up obligations for both Sponsor and subject will be explained at study 
entry, however a more detailed separate long term follow up consent form will also be provided 
at the time of completion (or early withdrawal) of this study. 
11.5 
Privacy and Confidentiality 
The collection and processing of personal and health data from subjects enrolled in this study 
will be limited to those data that are necessary to investigate the safety, efficacy, quality, and 
utility of the investigational study drug, and will be managed in accordance with U.S. Health 
Insurance Portability and Accountability Act (HIPAA) regulations. 
Each subject will be assigned a unique identification code at the time of study screening, and 
this code will be used throughout the study and follow up period to identify subject-specific 
data. As it will be important in long-term follow-up to identify the protocol subjects were 
initially enrolled to, the unique subject identification numbering system will contain references 
to the original protocol and site. Additionally, initials and date of birth of each subject will be 
collected to ensure the correct identification of laboratory data and archived blood and/or tissue 
samples to individual subjects. These data must be collected and processed with adequate 
precautions to ensure confidentiality and compliance with applicable data privacy protection 
laws and regulations. Appropriate technical and organizational measures to protect the personal 


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data against unauthorized disclosures or access, accidental or unlawful destruction, or 
accidental loss or alteration must be put in place. Sponsor personnel whose responsibilities 
require access to personal data agree to keep the identity of study subjects confidential. 
The informed consent obtained from the subject includes explicit consent for the processing of 
personal data and for the investigator to allow direct access to his or her original medical records 
for study-related monitoring, audit, IEC/IBC review, and possible regulatory inspection. This 
consent also addresses the transfer of the data to other entities and to other countries and use 
for publication. 
The unique study identification code will be able to be linked back to an individual subject 
identity only through the subject identification and enrollment log maintained by the 
investigator. Stored samples will only be used for the described exploratory analysis or 
investigation into a specific subject adverse event or other safety concern. If no further safety 
investigations have been required, the subject has the right to request their samples are 
destroyed after a minimum storage period of 15 years has expired. 
The subject has the right to request, through the investigator, access to his or her personal data 
and the right to request rectification of any data that are not correct or complete. Reasonable 
steps will be taken to respond to such a request, taking into consideration the nature of the 
request, the conditions of the study, and the applicable laws and regulations. 
12. ADMINISTRATIVE CONSIDERATIONS 
12.1 
Subject Screening and Enrollment 
The investigator will be required to maintain a log of pre-screening and screening activity, 
which provides de-identified details (initials and date of birth) for all potential subjects who 
were seen to determine suitability and eligibility for the study. 
All screened subjects (i.e. those subjects who signed consent and for whom a unique study 
identification number was assigned) will be recorded on a subject identification and enrollment 
log that permits easy identification of each subject during and after the study. This log will be 
treated as confidential, with the original held at the study site and no copy made for any purpose. 
The Ttn and HSPCtn manufacturing is specific to each individual study subject, and only one 
subject’s dosage forms can be manufactured at a time. Consequently, screening failures can 
have a significant detrimental effect on the manufacturing schedules for all participating 
subjects and for the study timelines over all. In order to minimize potential negative impact, 
concurrent screening of potential subjects is permitted to the extent that the total number of 
subjects in screening does not exceed the total number of available places within each cohort 
(i.e. a maximum of 4). Once a subject/subjects are determined to meet the Screening 1 eligibility 
criteria, they will progress to Screening 2 in order to confirm HIV RNA and CD4+ lymphocyte 
counts continue to be within the required range for eligibility. If there are multiple subjects who 


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have completed Screening 1, their order of progression to Screening 2 will be determined by 
the Sponsor, taking into consideration their medical history, Screening 1 laboratory results, and 
factors relating to their overall appropriateness for the study. 
12.2 
Source Documentation 
Source data comprises all information, original record of clinical findings, observations or other 
activities in a clinical trial, necessary for the reconstruction and evaluation of the trial. The 
author of an entry or record in the source documents should be identifiable. Any specific source 
data requirements will be reviewed with the investigator and investigational staff before the 
study and will be described in the monitoring plan (or equivalent document). 
12.2.1 Documentation of Eligibility 
At a minimum, source documentation must be available to confirm the study subject’s 
identification and eligibility. Documentation concerning previous ART regimens should 
include the start and stop dates, with documented reasons for cessation. The reasons for 
stopping ART are to be in accordance with the special considerations discussed in Section 11.1. 
The investigator must document what he/she considers to be a virologically-effective ART 
regimen option for each subject, including the basis for the selection. 
Historical CD4+ T lymphocyte records must be complete enough to give reasonable evidence 
that the CD4+ T lymphocyte count has been ≥ 250 cell/µl since HIV-1 diagnosis (with the 
exception of the period immediately following acute infection). 
12.2.2 On-Study Documentation 
At a minimum, the type and level of detail of source data for a study subject should be consistent 
with that commonly recorded at the site as a basis for standard medical care. Additionally, the 
source documentation must include study identification, dates of visits, study procedures 
performed, administration of the transduced cell product, results of safety and efficacy 
parameters as required by the protocol, record and follow up of all adverse events, concomitant 
medication, and date of study completion or reason for discontinuation (if applicable). A study 
subject is not obliged to provide a reason for their decision to withdraw (withdrawal of consent) 
from the study, however it is expected that the decision and due diligence in inquiry and follow 
up be documented. 
12.3 
Case Report Form Completion 
A Case Report Form (CRF) is provided for each individual study subject in electronic format. 
The study CRF is the primary data collection instrument for the study and the study data will 
be transcribed by study personnel from the source documents onto the CRF. All data recorded 
on the CRF must be substantiated by the source documents at the site. All missing data must be 
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Worksheets may be used for the capture of some data to facilitate completion of the CRF. Any 
such worksheets will become part of the source documentation for that subject. All data must 
be entered into the CRFs in English. 
Designated site personnel must complete the CRF as soon as possible after a study subject’s 
visit, and the forms should be available for review at the next scheduled monitoring visit. 
All CRF entries, corrections, and alterations must be made by the investigator or other 
authorized study-site personnel, as indicated on the sites delegation of responsibilities and 
signature log. Data queries will be generated by either the monitor or data management as 
necessary. The investigator or an authorized member of the investigational staff must adjust the 
CRF (if applicable) and complete the query. All changes to entered data must have a 
documented audit trail that allows identification of when and who made the data change. 
By signing the study completion page the investigator is attesting that all data recorded in the 
CRF is a complete and accurate record of the subject’s pre-study medical history and on-study 
observations and results. 
Data from exploratory analyses will not be captured in the study CRF. 
12.4 
Monitoring and Data Quality Assurance 
Monitoring will be performed by the Sponsor or contracted designee. The first monitoring visit 
will be performed as soon as possible, and not more than 2 weeks after screening of the first 
subject. Thereafter all screened subjects will be monitored to confirm eligibility prior to 
commencement of apheresis. At the completion of the screening to infusion phase of the study, 
routine monitoring will be performed on a regular basis until the last subject last visit is 
achieved and all data monitored. 100% source data verification will be performed to verify the 
accuracy and completeness of all data collected on the case report forms (CRF). On-site visits 
will be documented with a signed site visit log kept at the site. 
The site is required to maintain source documents that support subject eligibility and all data 
reported in the CRF. Direct access to source documentation (medical records) must be allowed 
for the purpose of verifying that the data recorded in the CRF are consistent with the original 
source data. If electronic records are maintained at the investigational site, compliance with 
CFR Part 11 and monitor access must be confirmed prior to study initiation at the site. The 
Sponsor expects that, during monitoring visits, the relevant investigational staff will be 
available, the source documentation will be accessible, and a suitable environment will be 
provided for review of study-related documents. The monitor will meet with the investigator 
and other applicable investigational staff on a regular basis during the study to provide feedback 
on the study conduct. 
Additional steps to be taken to ensure the accuracy and reliability of data include; the selection 
of qualified investigators and appropriate study center(s), training of the investigator and 


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associated personnel on the protocol and CRF completion before the study commences and 
throughout the study period as required per staff or protocol changes, and written instructions 
for collection, preparation, and shipment of blood, urine and tissue samples. 
12.5 
Record Retention 
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all CRFs 
and all source documents that support the data collected from each study subject, as well as all 
study documents as specified in ICH/GCP Section 8, Essential Documents for the Conduct of 
a Clinical Trial, and by the applicable regulatory requirement(s).  
Essential documents must be retained until at least 2 years after the last approval of a marketing 
application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region or until at least 2 years have elapsed since the formal 
discontinuation of clinical development of the investigational product. These documents will 
be retained for a longer period if required by the applicable regulations or by an agreement with 
the Sponsor. The investigator/institution will take measures to prevent accidental or premature 
destruction of these documents. Under no circumstance shall the investigator relocate or dispose 
of any study documents before having obtained written approval from the Sponsor. 
If it becomes necessary for the Sponsor or the applicable regulatory authority to review any 
documentation relating to this study, the investigator/institution must permit access. 
12.6 
Regulatory Review and Approval Process 
This protocol was submitted for review at the December 12-14, 2011 meeting of the National 
Institutes of Health (NIH) Recombinant DNA Advisory Committee (RAC), and will be 
conducted under an IND submitted to the FDA Center for Biologics Evaluation and Research 
(CBER). 
Pending approval of the protocol by RAC and CBER, submission will be made to the applicable 
Institutional Biosafety Committees (IBC) and Institutional Ethics Committees (IEC) for the 
selected sites. The protocol will not be initiated until all of the above federal and institutional 
approvals have been received. 
Amendments will be provided to RAC and CBER and will not be implemented until approval 
is received from both IBC and IEC at all selected sites. 
12.7 
Trial Committees 
12.7.1 Medical Review Committee (MRC) 
A medical review committee will be established to ensure that the safety of subjects 
participating in the study is not compromised. The MRC will include, but will not be limited 
to, at least two expert physicians in the area of HIV medicine and/or hematology. The MRC 
will include members from the Sponsor and external consultants. The MRC will monitor the 


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safety of the study by reviewing AE/SAE, clinical, and laboratory data in a regular and timely 
manner. Any grade three or four toxicities will be comprehensively reviewed and the MRC will 
be required to make formal recommendations. Specific recommendations concerning the dose 
of busulfan will be made by the MRC following assessment of post-conditioning hematopoietic 
recovery. Delayed hematopoietic recovery is defined as an ANC < 0.5x103/µL (mm3) and/or 
platelet count of < 25x103/µL (mm3) after 42 days post-infusion, and observation of this adverse 
event in any subject will prompt a reduction in the busulfan dose, as described in section 6.2.2. 
The MRC will communicate any occurrence of delayed hematopoietic recovery to the DSMB 
in real-time.  
The MRC will assess the hematopoietic recovery of every subject, and following completion 
of week 12 make formal recommendation if the back-up apheresis product is no longer required. 
With the agreement of the Principal Investigator, these samples may then be destroyed, or 
donated to research, in accordance with the subject’s wishes at time of study consent. 
The MRC will also be responsible for the review and/or input into the case narratives for 
SUSARs, including adjudication of possible causality to Cal-1 or study procedures.  
Details of the composition, roles, responsibilities, and relationship with the DSMB are 
documented in the MRC charter. 
12.7.2 Data Safety Monitoring Board (DSMB) 
An independent DSMB will be commissioned for this study to evaluate the risk/benefit of 
busulfan and to review all safety and selected efficacy (such as the degree of Cal-1 marking in 
peripheral blood, GALT and bone marrow) data from cohorts 1 and 2 prior to proceeding with 
the next planned cohort. Progression to each cohort is dependent on the positive 
recommendation of the DSMB. Details of the composition, roles, responsibilities and timelines 
will be documented in the DSMB charter. 
There are no formal statistical stopping rules, however the DSMB will have the responsibility 
for independently evaluating safety on the bases of there being no evidence of safety concern(s) 
to warrant study cessation. The occurrence of bone marrow failure (defined as a protracted 
neutropenia (ANC < 0.5x103/µL (mm3)) and/or thrombocytopenia (platelets < 25x103/µL 
(mm3)) after Week 12 post-infusion) will trigger a temporary hold on the administration of 
busulfan and subject enrolment pending a safety assessment by the DSMB. The occurrence of 
grade 4 laboratory abnormalities, unanticipated incidence, severity or frequency of AE/SAEs, 
or failure of Ttn/HSPCtn manufacturing processes may also be events that could present 
sufficient safety concerns to warrant study cessation. Following completion of the safety data 
review, the DSMB may also recommend that the study be modified to improve monitoring of 
safety, additional subjects be enrolled to assess safety, or the study be terminated for safety 
reasons. 


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In addition to scheduled review of Cohort data, the DSMB chairperson will receive a copy of 
all MRC recommendations and all SAE reports that have possible suspect causality to Cal-1 
and/or the study procedures in real time (i.e. at the same time as the MRC). The Chairperson is 
responsible for determining if a special meeting of the DSMB is required to review any event 
in further detail and make a recommendation between cohorts. Recommendations will be 
submitted to the Sponsor and authorities as required, according to local guidelines and 
regulations. 
12.8 
Protocol Amendments 
Neither the investigator nor the Sponsor will modify this protocol without a formal amendment. 
All protocol amendments must be issued by the Sponsor, and signed and dated by the 
investigator. Except when necessary to eliminate immediate hazards to the subjects, 
amendments must not be implemented without prior IEC/IRB approval. 
Documentation of amendment approval by the investigator and IEC/IRB must be provided to 
the Sponsor or its designee. When the change(s) involves only logistic or administrative aspects 
of the study, the IRB (and IEC where required) only needs to be notified. 
During the course of the study, in situations where a departure from the protocol is unavoidable, 
the investigator or other physician in attendance will contact the appropriate Sponsor 
representative (refer to protocol contact information page). Except in emergency situations, this 
contact should be made before implementing any departure from the protocol. In all cases, 
contact with the Sponsor must be made as soon as possible to discuss the situation and agree 
on an appropriate course of action. It is the responsibility of the investigator to document in the 
source documents any departure from the protocol, the circumstances requiring it, the action 
taken and the outcome. No waivers or exceptions to the study entry procedures or requirements 
will be granted. 
12.9 
Audits 
The Sponsor or assigned designees may visit the site at any time during or after completion of 
the study to conduct an audit of the study in compliance with the protocol and regulatory 
guidelines. These audits will require access to all study records, including source documents, 
for inspection and comparison with the CRFs. The investigator and staff are responsible for 
being present and available for consultation during scheduled site audit visits conducted by the 
Sponsor or its designees. 
Similar auditing procedures may also be conducted by agents of any regulatory body. The 
investigator should immediately notify the Sponsor if they have been contacted by a regulatory 
agency concerning an upcoming inspection. 
 
 


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12.10 Disclosure of Financial Interests 
12.10.1 Sources of Funding and Disclosure of Financial Interest 
This study is financed by Calimmune, Inc. Calimmune, Inc. is financially supported through 
private and corporate investment, and research grants. This study is partially funded by the 
California Institute of Regenerative Medicine. These funding sources had no role in the design 
of this protocol and will not have any role the conduct, analyses, interpretation of the data, or 
preparation of the study report. 
All principal and sub investigators and members of all trial committees (per section 12.7) will 
be required to complete a written declaration of potential financial interest, disclosing if they, 
their spouse, dependents, or other institution(s) they are affiliated with, have or receive from 
Calimmune, Inc.; 
- 
Honoraria or other form of material compensation which exceeds USD25,000 
- 
Grant support for institutional or personal research projects which exceeds USD25,000 
- 
Other research or business arrangement 
- 
Consultancy 
- 
Employment 
- 
Significant equity interest in the form of stock &/or employee stock options to the value 
of USD50,000 or more. 
- 
Any proprietary or financial interest in Cal-1, such as patent, trademark, copyright, 
royalty or licensing agreement 
- 
A financial arrangement for the conduct of Cal-1 clinical trials that provides explicitly 
greater payment for other compensation for a favorable outcome or decision 
12.10.2 Subject Payment and Compensation 
Study subjects will not be compensated for their participation in this study, except for 
reasonable travel-related expenses, which will be described in the participant information and 
consent form and approved by the IEC/IRB. 
12.11 Use of Information and Publication 
Neither the complete nor any part of the results of the study carried out under this protocol, nor 
any of the information provided by the Sponsor for the purposes of performing the study, will 
be published or passed on to any third party without the consent of the study Sponsor.  Any 
investigator involved with this study is obligated to provide the Sponsor with complete test 
results and all data derived from the study. The Sponsor will comply with the requirements for 
publication of trial results. 


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The results of this trial may be published or presented at scientific meetings. If this is foreseen, 
the investigator agrees to submit all manuscripts or abstracts to the Sponsor prior to submission. 
This allows the Sponsor to protect proprietary information and to provide comments based on 
information from other studies that may not yet be available to the investigator. 
In accordance with standard editorial and ethical practice, the Sponsor will only support 
publication of multicenter trials in their entirety and not as individual center data. In this case, 
a coordinating investigator will be designated by mutual agreement. 
Authorship will be determined by mutual agreement and in line with International Committee 
of Medical Journal Editors (ICMJE) authorship requirements.  Any formal publication of the 
trial in which input of Sponsor personnel exceeded that of conventional monitoring will be 
considered as a joint publication by the investigator and the appropriate Sponsor personnel.  
Data derived from analysis of stored blood and cell specimens on individual subjects will not 
be provided to trial investigators, except where explicitly stipulated in a trial protocol (e.g. if 
the result is an enrollment criterion) or related to investigation into an adverse event. Exceptions 
may be granted (e.g. if data would be linked to non subject-specific safety issues). The 
aggregate results of any research conducted using stored blood and cell specimens will be 
available in accordance with the effective Sponsor policy on trial data publication. 
Any inventions and resulting patents, improvements and/or know-how originating from the use 
of the stored blood and cell specimens will become and remain the exclusive and unburdened 
property of the Sponsor, except where agreed otherwise. 
All information concerning Cal-1 supplied by the Sponsor to the investigators and not 
previously published is considered confidential and remains the sole property of the Sponsor. 
The investigators agree to use this information only to accomplish this study and not for any 
other purpose without the Sponsor’s written consent. 
 


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(2007). Transfer of Autologous Gene-modified T Cells in HIV-infected Patients with Advanced 
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69. Younan PM, Polacino P, Kowalski JP, Peterson CW, Maurice NJ, Williams NP, Ho O, Trobridge GD, Von Laer 
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JS, Keating S, Lee TH, Li P, Murray D, Palmer S, Pilcher C, Pillai S, Price RW, Rothenberger M, Schacker T, 
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Efficient entry inhibition of human and nonhuman primate immunodeficiency virus by cell surface-expressed 
gp41-derived peptides. Gene Therapy, 15, 1210-22. 
 
 
 


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APPENDIX I  
DIVISION OF AIDS TABLE FOR GRADING THE SEVERITY OF ADULT ADVERSE EVENTS 
(PUBLISH DATE DECEMBER, 2004; CLARIFICATION AUGUST 2009) 
http://rsc.tech-res.com/safetyandpharmacovigilance/gradingtables.aspx 
General Instructions 
Estimating Severity Grade for Parameters Not Specifically Identified 
Determining 
Severity Grade for Parameters “between Grades” 
Definitions  
 
Basic Self-care Functions 
Activities such as bathing, dressing, toileting, transfer/movement, 
continence, and feeding.  
 
LLN 
Lower limit of normal  
 
Medical Intervention 
Use of pharmacologic or biologic agent(s) for treatment of an AE.  
 
NA 
Not Applicable  
 
Operative Intervention 
Surgical OR other invasive mechanical procedures.  
 
ULN 
Upper limit of normal 
 Usual Social & Functional Activities 
Adaptive tasks and desirable activities, such as going to work, shopping, 
cooking, use of transportation, pursuing a hobby, etc. 
 
GRADE 5: FOR ANY AE WHERE THE OUTCOME IS DEATH, THE SEVERITY OF THE AE IS CLASSIFIED AS GRADE 5.  
 
If the need arises to grade a clinical AE that is not identified in the DAIDS AE grading table, use the category “Estimating Severity Grade” located below.  
If the severity of an AE could fall under either one of two grades (e.g., the severity of an AE could be either Grade 2 or Grade 3), select the higher of the two grades for the AE.  
Values Below Grade 1 
Any laboratory value that is between either the LLN or ULN and Grade 1 should not be graded. 
CLINICAL 
PARAMETER 
GRADE 1 
GRADE 2
GRADE 3
GRADE 4
 
MILD 
MODERATE
SEVERE
POTENTIALLY
 
 
LIFE-THREATENING
ESTIMATING SEVERITY GRADE  
Clinical adverse event NOT 
identified elsewhere in this  
DAIDS AE grading table 
Symptoms causing no or minimal 
interference with usual social & 
functional activities   
Symptoms causing greater than 
minimal interference with usual social 
& functional activities 
Symptoms causing inability to 
perform usual social & functional 
activities 
Symptoms causing inability to 
perform basic self-care functions OR  
Medical or operative intervention 
indicated to  prevent permanent 
impairment, persistent disability 


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APPENDIX II 
 
PROHIBITED IMMUNOSUPPRESSION / IMMUNOMODULATION 
 
• Azathioprine 
• Cyclosporin A 
• Cyclophosphamide 
• Systemic Glucocorticosteroid therapy cumulative dose ≥ 210mg prednisolone, or equivalent, over a 
two-week period (e.g. oral prednisolone ≥ 15mg/day for 14 days or more). 
• Leflunamide 
• Methotrexate 
• Mycophenolate (mofetil or sodium) 
• All biological immunomodulatory agents (e.g. etanercept, infliximab, adalimumab, anakinra, 
natalizumab, etc.) 
• All immunostimulants (e.g. IL-2, Interferon-α or –β, other cytokine therapies) 
 
 
 


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2.1. Description of Overall Study Design and Plan ................................................................ 8
2.2. Objectives ....................................................................................................................... 8
2.2.1. Primary objective ................................................................................................................... 8
2.2.2. Secondary objective(s) ........................................................................................................... 9
2.3. Sample Size ..................................................................................................................... 9
2.4. Randomization and Assignment of Subjects to Treatment Groups ............................. 10
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ϰ͘ŶĂůǇƐŝƐWŽƉƵůĂƚŝŽŶƐ͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘ϭϯ
4.1. Population Descriptions ............................................................................................... 13
4.1.1. Enrolled Population ............................................................................................................. 13
4.1.2. Safety Population ................................................................................................................. 13
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5.1. Subject disposition ....................................................................................................... 14
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7.1. Demographics ............................................................................................................... 16
7.2. HIV-1 history ................................................................................................................. 16
7.3. Medical history ............................................................................................................. 16
7.4. Eligibility ....................................................................................................................... 16
7.5. Chest X-Ray ................................................................................................................... 16
7.6. ART Therapy History ..................................................................................................... 16
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8.1. Transduced CD4+ and CD34+ Cell Product Dose .......................................................... 17
8.2. CD4+ and CD34+ Apheresis .......................................................................................... 17
8.3. CD4+ and CD34+ Manufacturing .................................................................................. 17
8.4. Mobilization Therapy .................................................................................................... 17
8.5. Busulfan Administration and PK Data .......................................................................... 17
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ϭϬ͘WŚĂƌŵĂĐŽĚǇŶĂŵŝĐƐ;WͿ͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘ϭϵ
ϭϭ͘ĨĨŝĐĂĐǇ͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘ϮϬ
11.1. Cell Dose vs. Marking/Expression ............................................................................... 20
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11.2. Busulfan AUC (Cohorts 2 and 3) vs. Marking/Expression ........................................... 21
11.3. CD4+ and HIV-1RNA vs. Marking/Expression ............................................................. 21
11.4. Absolute Neutrophil Counts (ANC) and Platelets vs. Marking/Expression ................ 21
11.5. Lymphocyte Development and Chronic Inflammation vs. Marking/Expression ........ 22
ϭϮ͘^ĂĨĞƚǇ͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘Ϯϯ
12.1. Adverse Events ........................................................................................................... 23
12.2. Concomitant medication ............................................................................................ 23
12.3. Laboratory .................................................................................................................. 23
12.4. Vital Signs ................................................................................................................... 24
12.5. Physical Examination .................................................................................................. 24
12.6. Pregnancy Test ........................................................................................................... 24
12.7. Other Safety ................................................................................................................ 24
ϭϯ͘/ŵŵƵŶŽŐĞŶŝĐŝƚǇŶĚƉŽŝŶƚƐ͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘Ϯϱ
ϭϰ͘,ĂŶĚůŝŶŐŽĨDŝƐƐŝŶŐĂƚĂ͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘Ϯϲ
ϭϱ͘ŚĂŶŐĞƐƚŽƚŚĞWůĂŶŶĞĚŶĂůǇƐŝƐ͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘Ϯϳ
ϭϲ͘/ŶƚĞƌŝŵĂŶĚ&ŝŶĂůŶĂůǇƐŝƐ͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘Ϯϴ
16.1. Medical Review Committee (MRC) ............................................................................ 28
16.2. Data Safety Monitoring Board (DSMB) Analyses ....................................................... 28
16.3. Interim Analyses ......................................................................................................... 29
16.4. Final Analysis (End of Study). ...................................................................................... 29
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ϭϴ͘dĂďůĞƐ͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘ϯϭ
ϭϵ͘>ŝƐƚŝŶŐƐ͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘ϯϮ
ϮϬ͘&ŝŐƵƌĞƐ͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘ϯϰ
Ϯϭ͘ZĞĨĞƌĞŶĐĞƐ͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘ϯϲ
ϮϮ͘ƉƉĞŶĚŝǆ/͗^ƵŵŵĂƌǇŽĨWƌŽƚŽĐŽůŚĂŶŐĞƐ͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘͘ϯϳ
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Protocol Section 
Nature of Change 
Rationale 
Contact information 
Update 
Glossary of terms 
Update/addition 
New terms added.  Changed SUA to SUSAR. 
Synopsis 
Addition 
Added clinical trials.gov registration number 
Added participating countries (USA). 
Update 
All units for laboratory values were updated to ISO 
(conventional) format for consistency. 
Schedule of Events 
Modification & 
addition 
Separated tables to pre-infusion and post-infusion 
Pre-infusion: 
1.  Added option pre-screening to help facilitate selection 
of suitable potential subjects and reduce the screen- 
fail rate 
2.  Separated consent procedure to ensure consent 
obtained prior to pre-screening 
3.  Increased window period for Screening 1 visit to assist 
sites in the consenting and scheduling of concurrent 
subjects for screening 
4.  Moved co-infection screening to Screening 1 due to 
better accommodate assay turn-around times and the 
Screening 2 window period 
5.  Added busulfan PK monitoring in response to FDA and 
DSMB request 
6.  Increased the window between CD34 apheresis and 
Baseline visit to better accommodate the turn-around 
time for product release testing 
Post-infusion: 
1.  Added ‘Conditioning F/U’ visits at week 0.5, 1.5, 2.5, 3, 
3.5, 4.5, 5, and 5.5 time points to increase intensity of 
post-conditioning and transplant subject safety 
monitoring in response to FDA request and in line 
with DSMB recommendations 
Footnotes: 
1.  Updated in line with above changes and change to 
lymphocyte phenotyping studies (see section 7.5). 
2.  Added unscheduled HIV-1 tropism assessment if 
subject discontinues the study post-infusion to 
recommence ART (see section 6.2.4) 
3.  Added stored EDTA-plasma sample for HIV viral load 
batch analysis (see section 7.5). 
CCI


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Protocol Section 
Nature of Change 
Rationale 
1.1 Background 
Addition 
In vivo studies added to section 1.1.1. 
Additional references cited section 1.1.2 literature 
update. 
Additional references cited section 1.1.2 (busulfan) 
regarding the use of low and intermediate doses of 
busulfan for non-myeloablative and reduced-intensity 
conditioning effects. 
3. Objectives and 
Outcome 
measures/endpoints 
Modification 
Update in line with changes to lymphocyte phenotyping 
studies (per section 7.3). 
4.Overview of study 
design 
Modification 
Updated timeline schematic in line with changes to the 
pre-infusion schedule of events. 
Updated DSMB recommendations to include Cohort 3 
proceeding with an increased dose of 6 to 8mg/kg 
busulfan (See section 6.2.2) 
5.2 Exclusion criteria 
Modification 
Ex-A updated to be in ISO units 
Ex-N modified to specify venous assessment prior to 
Screening1, to allow flexibility in scheduling. 
5.4 Rescreening 
Modification 
Re-screening procedures were adjusted in line with the 
changes to Screening 1 and Screening 2 procedures. 
6.1.3 
Dosage and 
administration 
Modification 
The order of infusion was changed to administer the 
HSPCtn first. This was a safety consideration, as an 
adverse reaction to the infusion products is potentially 
more likely with the Ttn. HSPCtn are the priority infusion 
for subjects who have received busulfan conditioning. 
The order of infusion for Cohort 1 subjects was Ttn, 
followed by HSPCtn. 
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Protocol Section 
Nature of Change 
Rationale 
6.2.2 Busulfan 
Modification 
The dosing range for busulfan was modified to include 
6mg/kg within the ‘moderate dose’ cohort (III). Dose 
adjustment rules, based on observation of delayed 
hematopoietic recovery were added. These changes are 
an additional safety precaution to ensure the dose of 
busulfan does not result in a more severe myeloablation 
than intended. The description of the busulfan dosing 
was corresponding updated throughout the protocol. 
As a safety precaution to ensure there would be 
sufficient CD34+ cells to ‘rescue’ a subject in the event of 
busulfan-induced myeloablation, a clause was added that 
busulfan will not be administered if the minimum 
anticipated HSPCtn dose (0.5x108 total CD34+ cells) is not 
achieved. 
If cell infusion is postponed, the administration of 
busulfan will also be postponed. Busulfan will be given 2 
days prior to the revised planned cell infusion date 
(baseline visit) with the contingent that all release criteria 
were met. 
6.2.3 
Post-busulfan 
infection prophylaxis 
Addition 
New section added to include specification on the post- 
conditioning infection prophylaxis regimen. Details of 
agents, doses and duration are provided. 
6.2.4 
Antiretroviral Therapy 
Addition 
HIV-1 tropism will also be performed if a subject is 
required to recommence ART post-infusion. 
7.1.1 Consent 
Addition 
New section created to align with the re-design of the 
schedule of events. Details are provided on the permitted 
timing of study consent. 
7.1.2 Pre-screening 
Addition 
New section created to align with the re-design of the 
schedule of events. The pre-screening visit is an optional 
visit included to assist sites in the selection of potential 
suitable subjects to participate. Consent requirements, 
optional visit procedures/laboratory tests and timing are 
described. 
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Protocol Section 
Nature of Change 
Rationale 
7.1.3 Screening 1 
Modification 
A screen fail rate of > 50% was experienced with Cohort 
1. Screen failures present a risk and inconvenience to 
study subjects and also increase study timelines. The 
timing of Screening has been adjusted to allow a 
maximum 3 month interval between consent and 
Screening 1 (increase from 2 months) to allow sites more 
time to obtain and evaluate pre-existing medical history 
as part of eligibility and suitability determination. 
Procedures were revised to include the co-infection 
screening and chest x-ray (moved from Screening 2). This 
was to simplify the screening 2 procedures, to minimise 
the risk of late notice screen fails and therefore reduce 
impact on both the individual subjects and the 
manufacturing facility preparation. 
A window period was added for the venous assessment, 
to allow this to be performed any time between consent 
and Screening 1. This will improve subject convenience, 
and also enable assessment of this eligibility criterion 
before the more invasive assessments are performed. 
Medical history instructions were expanded to specify 
collection of vaccination, drug allergy and recurrent 
infection history, in line with standard bone marrow 
transplant procedures 
7.1.4 
Screening 2 
Modification 
Window period modified to be within 1-2 weeks of CD4 
apheresis. 
Window between Screening 1 and Screening 2 modified 
to 2-12 weeks to allow concurrent screening (within 
limitations specified in Section 12.1). 
Visit laboratory tests simplified to confirmation of HIV-1 
RNA and CD4+ eligibility criteria. Chest x-ray and co- 
infection screening moved to Screening 1 because of 
assay turn-around times. 
7.1.5 
CD4+ T lymphocyte 
apheresis 
Modification & 
addition 
Added subject’s weight to be measured and provided to 
the manufacturing lab to enable calculation of the 
anticipated dose for the finished Ttn product. 
 
 
 
 
Removed description of tests to be performed on the 
collected apheresis product, as these are manufacturing- 
specific procedures. 
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Protocol Section 
Nature of Change 
Rationale 
7.1.7 
CD34 + apheresis 
Modification & 
addition 
Added subject’s weight to be measured and provided to 
the manufacturing lab to enable calculation of the 
anticipated dose for the finished HSPCtn product 
 
 
 
 
 
 
Removed description of tests to be performed on the 
collected apheresis product, as these are manufacturing- 
specific procedures. 
7.1.8 
Administration of 
busulfan 
Modification & 
addition 
Added stipulation that this visit can only occur after 
confirmation that the Ttn and HSPCtn products have been 
released and are available on site 
Clarified the timing of each busulfan dose to be in the 
morning 
Added instruction in the event of a delay in the planned 
cell infusion (Baseline) visit 
Added specification for collection of blood samples and 
batch testing for busulfan PK monitoring. 
7.1.9 
Baseline (day of 
infusion) 
Modification 
Removed the provision to postpone the infusion if 
busulfan conditioning has occurred 
 
 
7.2.1 
Conditioning follow 
up 
Addition 
New section to describe the content and timing of 
additional visits to increase intensity of post-conditioning 
and cell-infusion safety monitoring. Both laboratory and 
clinical monitoring is specified 
Extended or more frequent safety follow up is permitted 
if clinically indicated for any study subject. 
7.2.2 Weeks 1, 2, 6, 8, 
16 & 20 
Addition 
Provision to perform a local STAT CBC/differential has 
been added to Weeks 1, 2 and 6, in line with conditioning 
follow up visits in section 7.2.1 
Safety limits are provided, along with appropriate steps 
to ensure subjects are further evaluated and – as 
necessary – treated by an experienced, accredited 
transplant center. 
7.2.3 Week 4 
Addition 
Provision to perform a local STAT CBC/differential has 
been added, in line with conditioning follow up visits in 
section 7.2.1 
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Protocol Section 
Nature of Change 
Rationale 
7.3 Safety evaluations Modification & 
addition 
C46 immunogenicity studies were moved from 
exploratory analysis (Section 7.6) to safety, in line with 
FDA request to perform these studies as part of the Cal-1 
safety data collection. 
7.5 
Efficacy evaluations 
Modification & 
addition 
Lymphocyte phenotyping studies have been added and 
grouped under the heading of ‘Lymphocyte development 
studies’. In addition to the thymopoiesis analysis, these 
now include ‘maturation’ and ‘inflammation’ to expand 
potential data on the impact of Cal-1 on lymphocyte 
dynamics. An additional baseline time point at the CD4+ 
apheresis visit was added to obtain baseline prior to 
apheresis and G-CSF mobilization. 
Potential cross-reactivity with Cal-1 in HIV-1 viral load 
assays has been identified as an area for further 
laboratory investigation. The HIV-1 RNA plasma assay 
details have been updated with the addition of a stored 
EDTA-plasma sample for the purposes of batch analysis 
with an alternative FDA approved plasma HIV-1 RNA 
assay, pending the outcome of these investigations. 
Corresponding updates to the Schedule of Events, visit- 
specific procedures and statistical analysis have been 
made for consistency throughout the protocol. 
7.6 
Exploratory 
evaluations 
Modification & 
addition 
 
 
 
 
 
 
 
 
 
 
 
7.7 Specimen storage Modification 
Storage of blood and tissue samples was previously 
described within the exploratory evaluations section. This 
has been moved into a separate section for clarity. 
Priority of use of the stored specimens has been clarified. 
10.1.4 
Modification 
The term Serious Unexpected Associated (SUA) Adverse 
Event was replaced with Serious & Unexpected 
Suspected Adverse Reaction (SUSAR) to be consistent 
with regulatory guidance and other study-related safety 
operational documentation (such as the DSMB charter 
and safety management plan) 
The term SUSAR replaces SUA throughout the protocol 
for consistency. 
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Protocol Section 
Nature of Change 
Rationale 
11.2 
Ethical and regulatory 
information 
Addition 
Details of the IND # and clinicaltrials.gov registration 
were added 
DSMB recommendation was added to the list of 
informational study updates to be provided to 
investigators. 
11.5 
Privacy and 
confidentiality 
Addition 
Reference to adherence to HIPPA regulations was added. 
12.1 
Subject screening and 
enrolment 
Addition 
Provision has been added to allow the concurrent 
screening of subjects in order to minimize the potential 
negative impact of screen failures on the participating 
subjects, sites and manufacturing schedules. The total 
number of subjects in screening at any time cannot 
exceed the number of available places within the cohort. 
Details on the timing and scheduling of subject visits is 
addressed. 
Consequent changes to the schedule of events and visit 
specific information are addressed throughout the 
protocol for consistency. 
12.7.1 MRC 
Addition 
Specification was added for the MRC review of 
hematopoietic recovery post busulfan and for the MRC to 
document their recommendation concerning an 
adjustment of the busulfan dose within the range 
specified. 
12.7.2 DSMB 
Addition 
Bone marrow failure has been defined by hematologic 
parameters and added as a stopping rule in addition to 
the events previously listed. Provision is also added for 
the DSMB chairperson to receive copies of MRC 
recommendations in real-time, and scope added to 
convene a special meeting of the DSMB and 
recommendations to be made between formal cohort 
reviews. 
12.10.1 
Sources of funding 
and disclosure of 
financial interest 
Modification 
Section updated to include information on source of 
Calimmune financial support, including disclosure of a 
CIRM grant. 
Appendix I 
Modification 
In order ensure up to date information, the DAIDS 
grading tables have been deleted and replaced with a link 
to the on line published document. The current version is 
December 2004, with clarifications dated August 2009. 
Specific guidance for values below Grade 1 have been 
added, in line with the DAIDS instructions. 
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Protocol Section 
Nature of Change 
Rationale 
Appendix III 
Modification & 
addition 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix IV 
Modification 
Section 3 
-  updated with details on prophylactic medications, dose 
and timing 
-  flow rate reduced to deliver total dose over 4 hours 
Section 5 updated with medications list. 
Appendix V 
Modification & 
addition 
Specific apheresis collection parameters provided for 
both CD4+ and CD34+ collections. 
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Protocol Section 
Nature of Change 
Rationale 
Schedule of events 
Removed 
footnotes referring 
to 4-week acute 
and 12-week sub- 
acute data time 
points 
Busulfan PK 
monitoring 
footnote revised 
Additional column 
for busulfan (Day - 
3) 
Footnote 18 
(unscheduled HIV- 
1 tropism) deleted 
Additional visits: 
Week 28, 36 & 44 
Original footnotes were potentially misleading. It is 
intended that data inclusive to Week 12 (not only weeks 
4 and 12) to be presented to the DSMB. 
Details on PK sampling now described in Appendix IV. 
Additionally, it was clarified that for Cohort 3, the busulfan 
dosing will start on Day -3 (and therefore completing at 
the same time relative to infusion as Cohort 1). 
Corresponding updates to text made throughout the 
document to correct references to Day -2 and Day-3 
Additional column added to separate the 2 days of 
busulfan and highlight the difference between cohorts 2 
and 3 
Unscheduled HIV-1 tropism no longer to be performed. 
Footnote 19 (Plasma HIV-1 RNA) renumbered to 18 
Additional visits in the final 12 weeks of the follow up 
period have been added so the frequency of follow up 
remains 4-weekly. The rationale for this change is that 
ongoing monthly follow up intervals allows closer follow 
up of HIV-1 viral load and CD4+ T-cell counts. 
3. Objectives & 
Outcome 
measure/Endpoints 
Secondary efficacy 
data description 
modified 
Format change to better describe evaluation of 
lymphocyte inflammation studies (separate bullet point 
from thymopoiesis and maturation). 
Various text updates then required throughout for 
consistency. 
4.1 Overview 
Minimum 
number of 
subjects per 
cohort reduced 
from 4 to 3. 
DSMB review 
consequently will 
proceed on data 
from 3 subjects, 
with an option for 
a fourth subject if 
requested. 
There has been a higher than expected screen failure rate 
(70%) and correspondingly an overall delay in study 
timelines. The original subject numbers were not based 
on formal power considerations, and no major safety 
concerns have presented to date. Thus, the change in 
sample size is being made in order to restore study 
timelines, yet not significantly impacting the probability 
of obtaining meaningful safety data from the study. 
Various text updates then required throughout for 
consistency. 
CCI


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Protocol Section 
Nature of Change 
Rationale 
5.1 General 
Considerations 
Timing for 
commencement 
of each 
subsequent 
cohort revised 
Screening for the next cohort will not commence until 
after the data for 3 subjects to Week 12 of post-infusion 
follow up is available for the DSMB review. 
6.2.2 Busulfan / 12.7.1 
MRC / 12.7.2 DSMB 
Text changes for 
consistency. 
Busulfan dose adjustment and temporary hold on further 
dosing had been included in the protocol with version 3.0 
changes. There were however small inconsistencies 
between the relevant sections that have now been 
addressed, and both dose adjustment or a hold on dosing 
are possible options for the MRC and DSMB in the event 
delayed hematopoietic recovery or/and bone marrow 
failure is observed with any subject. 
6.2.4 Antiretroviral 
Therapy 
Specific 
instructions added 
with respect to the 
confirmatory re- 
test in the event 
that s subjects HIV- 
1 viral load 
exceeds the 
specified safety 
limit. 
Cross-reactivity with the Cal-1 vector has been 
demonstrated in the Roche COBAS® AmpliPrep/COBAS® 
TaqMan® HIV-1 RNA PCR assay. Because this cross- 
reactivity has the potential to artificially elevate viral load 
results, the confirmatory assay is to be performed with 
an alternative HIV-1 assay (Abbott RealTiŵe m2000), 
which does not appear to cross-react with the Cal-1 
vector. To ensure accurate interpretation of results, 
complete batch analysis of all time points is specified in 
the event a confirmatory re-test is required. 
Abbott RealTiŵe m2000 batch data will be used for 
formal analyses. 
7.1.8 Administration 
of Busulfan 
Details of PK 
sampling removed 
Details on sampling have been removed from this section 
and now described in Appendix IV. 
7.3 Safety Evaluations Reference to RCL 
biological assay 
removed 
As both Cal-1 vector and the disease indication are a 
lentivirus, biological RCL assay is not technically feasible. 
7.5 Efficacy 
Evaluations 
Details of cross- 
reactivity updated, 
with specific 
alternative assay 
added 
Further details on 
Cal-1 marking 
&expression added 
Cross reactivity with Cal-1 has been confirmed and the 
Abbott RealTiŵe m2000 assay has been identified as a 
suitable alternate assay for batch analysis. 
Clarified the PCR targets for monitoring of Cal-1 presence 
and activity 
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Protocol Section 
Nature of Change 
Rationale 
8. Subject 
Withdrawal/Discontin 
uation 
Definition of 
discontinuation 
and withdrawal 
clarified 
Discontinuation has been clarified as referring to the 
population of subjects that are discontinued from 
secondary analysis due to commencement of ART or 
other prohibited concomitant medication. These subjects 
continue in safety follow up. 
Withdrawal has been clarified as referring to the 
population of subjects that have ceased study 
participation. 
Various text updates then required throughout for 
consistency, particularly section 9.1. 
9. Statistical Methods Power calculations 
updated with new 
subject numbers 
Changes to text within the Safety and Key Efficacy 
sections made to include power calculations for 3 
subjects per cohort as well as 4 
9.1 Statistical Analysis Clarification on 
which assay data 
to be used in 
formal analyses 
Formal statistical analysis will be performed using the 
batch data from the Abbott assay. 
12.7.2 DSMB 
Clarification added 
regarding data for 
DSMB review and 
scope of 
recommendations 
Removed reference to acute and sub-acute time points 
(per Schedule of Events), and revised section text 
accordingly. Added description of the potential scope for 
DSMB recommendation to include improved safety 
monitoring, study modification, additional subject 
recruitment and termination. 
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Protocol Section 
Nature of Change 
Rationale 
Appendix IV 
PK sampling 
information added 
Other significant 
changes made to 
improve safety and 
enhance clarity for 
implementation 
PK sampling moved from section 7.1.8 to include 
together with other instructions on the administration 
and monitoring of busulfan. The PK sampling schedule 
was improved with additional collection time points. 
Additionally, the site for PK blood draw details were 
expanded to increase consistency across sites in 
collection and handling of samples. 
For logistical reasons, a window period of 3 days prior to 
Day -2 has been added for subject’s weight for the 
purposes of busulfan dose calculation. 
Changes to the busulfan preparation, administration and 
monitoring include: 
- 
Adjusted ideal body weight dose calculation, and 
specification on value to use for dose calculation. 
- 
Further specifications provided to provide clarity 
for pharmacists and clinical staff (e.g. use of an IV 
tube filter, infusion timing, IV placement etc.). 
- 
For operator safety, the IV line is to be primed 
with saline (not busulfan), and an over-fill has 
been added to the infusion volume to adjust for 
the IV line volume. 
- 
Needle size and infusion time reduced in line 
with standard practice. 
- 
Lorazepam replaced with levetiracetam 
(Keppra™) as the prophylactic agent for busulfan- 
induced seizure. Levetiracetam is less sedating 
and provides safe and stable seizure prophylaxis. 
-     Extended anti-emetic medication to include PRN 
oral dosing in addition to IV pre-medication. 
- 
Timing of vital signs adjusted to make more 
consistent though the total infusion and PK 
period. 
- 
Specified additional prohibited concomitant 
medications that may interfere with busulfan 
clearance. 
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Protocol Section Nature of Change Rationale 
Section 6.1.1 
Section 6.1.3 
Appendix III 
Update 
anticipated dose 
of Ttn (cell 
numbers and 
volume) 
 
 
 
 
 
 
 
 
 
 
Section 6.1.1.2 
Section 6.2.2 
Section 7.1.8 
Section 7.1.9 
Appendix III 
CD34 minimum 
dose revised 
Previously expressed as a total number of cells, the 
minimum dose of HSPC required to proceed with 
busulfan conditioning has been revised to be expressed 
as a dose per kg of subject weight. 
An aliquot of 1x106 CD34+ cells/kg will be cryopreserved 
prior to ŝŶǀŝƚƌŽmanipulations with the manufacture of 
the HSPCtn dose. These reserved cells will be 
administered of the HSPCtn dose is less than 
2x106/kg. 
Section 7.1.4 
Updated 
description of 
timing between 
Screening 1 and 
2 
Inconsistency between protocol text and SOE 
addressed by updating section 7.1.4 wording 
Section 7.1.8 
Appendix 
III 
Appendix 
IV 
O2 saturation 
included in 
busulfan infusion 
observations 
Vital sign monitoring to include O2 saturation during the 
actual infusions, but not required during the PK 
collection period. Subjects to continue to be visually 
monitored during this period, with vital signs to be 
measured as clinically indicated. 
Section 7.2.4 
Section 8 
Schedule of 
Events 
Appendix V 
Addition of a pre- 
busulfan 
assessment visit 
A scheduled study visit allows for more 
comprehensive safety assessment prior to 
commencement of busulfan 
CCI
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Protocol Section Nature of Change Rationale 
Section 7.5 
Update 
description of 
batch analysis 
using the Abbott 
HIV viral load 
assay 
Inconsistency between protocol text and SOE footnotes 
addressed by updating section 7.5 wording 
Section 8 
Schedule of 
Events 
Addition of 
withdrawal/disco
ntinuation visit 
A withdrawal/discontinuation visit allows timely 
capture of important safety and efficacy data at 
the time of subject withdrawal/discontinuation 
visit. 
Appendix IV 
Updated list of 
contraindicated 
medications 
Removed 
specification for 
IV size for PK 
sampling 
Azithromycin added to the list of contraindicated 
medications as it may significantly slow busulfan 
clearance. 
Specification for a 22 gauge IV for the PK sampling 
has been removed, allowing the site discretionary 
choice of the IV size 
CCI


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Protocol 
Nature of Change 
Rationale 
SOE 
5.4/5.5 
6.1.2 
7.1.5 
8 
Permit repeat of small 
volume apheresis in 
event that the initial Ttn 
manufacturing is not 
successful or some 
other event prevents 
release or infusion of 
the product. 
Multiple, small volume aphereses are performed in clinical 
practice following sufficient time for PBMCs to return to pre- 
apheresis levels (~ 4weeks). In event of a manufacturing 
incident, this provision would allow a subject the option to 
consent to the repeat apheresis and continue in the study. 
SOE 
5.3 
5.4/5.5 
6.1.2 
6.2.1 
7.1.7 
8 
Permit repeat of G-CSF 
mobilization and large 
volume apheresis in 
event that the initial 
HSPCtn manufacturing is 
not successful or some 
other event prevents 
release or infusion of 
the product 
Repeat apheresis procedures are performed in clinical 
practice following sufficient time for hematopoietic stem 
cells to return to pre-apheresis levels (~ 4weeks). In event of 
a manufacturing incident, this provision would allow a 
subject the option to consent to the repeat procedures and 
continue in the study. 
5.2 
Redefinition of the HIV 
RNA (viral load) lower 
and upper limits of 
eligibility to account for 
normal variability of the 
assay 
The viral load assay can have a standard variability of 0.2 
log10. Amended inclusion criteria G to specify “Plasma HIV-1 
viral RNA ≥ 5,000 copies/ml +/0.2 log10 and ≤ 100,000 
copies/ml +/- 0.2 log10 at Screening 1 and Screening 2 (≥ 
3,200 copies/ml and ≤ 160,000 copies/ml)”. Improves the 
screening process without impact on subject characteristics 
and safety. 
SoE 
7.1.4 
Inclusion of chemistry 
panel in Screen 2 visit 
Feedback from apheresis units has been that electrolytes 
required within at least 2 weeks of planned apheresis to 
assist with apheresis settings. Inclusion in the study visit (and 
consequently central lab arrangement) simplifies procedures 
for the site and subject. 
In the event that Screening is performed > 2 weeks prior to 
the planned apheresis, there is now provision for the site to 
perform local lab CBC/differential with platelets and serum 
electrolytes. 
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Protocol 
Nature of Change 
Rationale 
SoE 
5.2 
7.1.4 
7.1.5 
‘Uncoupling’ of Screen 
2 visit from 
commencement of 
apheresis procedures 
In practice, there are a number of factors that can impact 
scheduling for apheresis. The protocol requirement to link 
Screening to the apheresis visit was often creating stress on 
the study participants as well on the clinical, apheresis and 
laboratory facilities involved, because eligibility was not 
confirmed until all laboratory tests results were reported.  By 
removing the 2-week time stipulation, there is greater 
flexibility and time for study sites to receive results of labs 
confirming subjects’ eligibility and scheduling of apheresis 
visit with their apheresis units, thus improving logistics for 
the sites, without impact on subject safety. 
The need to have recent CBC and electrolyte data for 
apheresis settings has been addressed by the inclusion of an 
additional supplementary (‘Pre-apheresis’) visit if Screening 2 
is performed >2 weeks prior to the planned apheresis. 
SoE 
6.2.2 
7.1.8 
Increased timing of pre- 
busulfan visit to up to 7 
days 
Improves logistics for the sites and subjects, without impact 
on subject safety. 
Appendix IV 
Change nausea 
prophylaxis dose from 
16mg IV Ondansetron 
(Zofran™) to 
8mg IV prior to 
busulfan then, post- 
busulfan 4mg to 8 mg 
orally every 8 hours as 
needed for nausea, not 
to exceed a total dose 
of 24 mg in 24 hours. 
Maximum ondansetron dose in 24 hour period is 16 mg 
(stated in the product information). Upon further review of 
current practice for stem cell transplant procedures, the new 
dosing schedule has been advised not to exceed 24mg in 24 
hours. This dosing schedule has been advised and approved 
by the Sponsor Medical Review Committee, and allows 
follow up oral dosing as required, thus potentially improving 
management of potential nausea secondary to the busulfan. 
SoE 
7.2.2 – 7.2.6 
Additional peripheral 
blood marking and 
expression studies at 
Weeks 1, 2 and 6 
Additional time points allow for better monitoring in the 
early post-transplant period 
Appendix I - V 
Removed provision to 
update appendix 
without a formal 
protocol amendment 
This provision has been removed to improve protocol 
version control. This change was requested by one study 
site’s IBC. 
Appendix IV 
Modified instructions 
for storage of diluted 
busulfan for 
intravenous infusion 
Busulfan diluted in saline for infusion has a limited stability 
period (approximately 12 hours with refrigeration). 
Instructions modified to recommend refrigerated storage of 
diluted busulfan to maximize stability. Stability information 
added for pharmacy and site reference. 

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Protocol 
Nature of Change 
Rationale 
Appendix V 
Added provision for use 
of central venous 
access for apheresis, if 
clinically indicated 
Short term central venous catheter placement is included as 
an option for subjects in whom it is clinically indicated to 
improve apheresis collection conditions and/or outcome. 
CCI


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Protocol Section Nature of Change 
Rationale 
Contact 
Information 
Updates 
Changes to sponsor and vendor staff and contact details 
Glossary of 
Abbreviations 
New information 
Additional abbreviations added 
Schedule 
of Events: 
Pre- 
infusion 
Changed use of 
‘Baseline’ 
to ‘Day 0’ 
Change to various 
visit names 
Changed 
how 
window period for 
Screening 
2 
expressed 
Additional new line 
items, per protocol 
changes Specimen 
storage time point 
added 
HIV monitoring tests 
added to pre-
busulfan assessment 
visit 
Avoid confusion with analytical baseline reference points, 
such as Screening. Changes made throughout protocol text 
for consistency Updated visit names around mobilization and 
conditioning for consistency and clarity 
Change for clarity only 
Line items for plerixafor, and pre-emptive HLA typing added. 
Specimen storage added to pre-busulfan assessment visit to 
enable 
collection of pre-conditioning ‘baseline’ storage samples 
Additional CD4+ T lymphocyte panel and HIV-1 RNA in 
order to gain a more timely pre-conditioning and pre-
infusion reference value. 
Schedule of 
Events: 
Post- 
infusion 
Change to various 
visit names 
New visit 
Updated visit names around post-busulfan monitoring for 
consistency and clarity and changed how the window 
period/visit schedule is expressed for clarity only 
Follow-up Extension added 
Section 4 
Schematic updated 
Schematic of overall study timeline updated to include 
changes to mobilization and apheresis procedures, as well 
as addition of the follow up extension. 
Section 4.2.1 
Change to 
apheresis 
rationale 
Summary description of yields to date, providing 
rationale for proposed mobilization and apheresis 
schedule changes. 
Section 4.2.3 & 
7.2.7 
New section (Follow-Up 
Extension) 
Addition of an ‘extension phase’ for up to 12 months after 
Week 
48 to allow ongoing monitoring of HIV data after Week 48 in 
subjects who complete to Week 48 off ART. 
If a subject had resumed ART prior to week 48, but then 
again stopped ART prior to Week 48, they would remain 
eligible to participate in the extension. 
Various updates to language throughout for 
consistency and subsequent subsection re-numbered. 
CCI


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Protocol Section Nature of Change 
Rationale 
Section 5.2 
Wording change to In-E Re-phrased the term ‘viable ART’ to ‘virologically-effective 
ART’ for 
clarity. 
Section 5.3 
Change to Ex-P 
Wording change to Ex-V 
Expanded to include NSAIDS in the contraindicated 
medications around the period of mobilisation, apheresis. 
Expanded to include the 6 week period post-busulfan 
conditioning 
Change reference to ‘baseline’ to ‘cell infusion (day 0)’ 
Section 5.5 
Changes to provisions 
for repeat procedures 
Expanded potential criteria for repeat of apheresis or 
mobilization/apheresis procedures to include the event 
that the minimum HSPCtn dose (2.0x106/kg) is not 
achieved, or failure of storage or shipment conditions (per 
changes to section 6.1) 
Simplified and clarified instructions and timing in the 
event of a process repeat. 
Section 6.1.1.2 
& 
6.1.3 
Increase dose on 
un- 
manipulated 
back-up apheresis 
product. 
Change HSPCtn 
anticipated dose to a 
required minimum 
dose. 
The back-up apheresis product is increased from 1x106 
CD34+ cells/kg to 1.2x106 CD34+ cells/kg to make allowances 
for potential losses during the freeze/thaw and 
administration process. Increasing the cell number is not 
expected to deplete the final HSPCtn dose, as this product is 
cryopreserved prior to CD34+ selection/purification. 
Further to experience with 4mg/kg busulfan in Cohort 2, 
and the degree of hematopoietic impact observed, a 
minimum dose of 
2.0x106 HSPCtn/kg has been specified. This is in line with 
common 
bone marrow transplant standards, and also enables 
preservation of the back-up apheresis product for rescue 
purposes, if required. Various updates throughout for 
consistency with this change. 
Section 6.2 & 
12.7.1 
Modification to the 
‘back- up’ apheresis 
product preparation 
and intention for use. 
With the change to specify a minimum 2.0x106/kg HSPCtn 
dose, the back-up apheresis product is now intended to be 
retained for the treatment of delayed hematopoietic 
recovery, or bone marrow failure should that occur in any 
subject. 
Subjects will be asked at time of initial consent to indicate if 
they want their back-up apheresis product to be destroyed 
or donated to Calimmune for research purposes if it is not 
required (based on recovery status at 12 weeks post-
infusion). 
Various updates throughout and Appendix III for 
consistency with this change. 
CCI


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Protocol Section Nature of Change 
Rationale 
Section 6.3.2 
New section for 
addition of plerixafor 
as a mobilizing agent. 
Plerixafor can result in up to 2-fold increase in CD34+ cell 
yields during apheresis; such a boost in CD34+ cell yields will 
maximise the potential HSPCtn dose as well as minimise the 
possibility of not achieving the minimum target dose. 
Use of a single dose of plerixafor on Day 4 of G-CSF after the 
first apheresis and as late as possible in the day to aim for 
dosing within 
16 hours of the next apheresis. Potential short-term gastro- 
intestinal side-effects will be limited by use of a single dose 
and managed with anti-diarrhoeal and anti-emetic 
medications. Various updates throughout for consistency 
with this change and renumbering of subsequent sections. 
Section 6.3.3 
Inclusion of provision for 
HLA typing. 
Increased busulfan dose 
range from 6-8mg/kg to 
4- 
8mg/kg given as 2 doses 
of 2, 3 or 4mg/kg. 
Provision is added at the pre-busulfan assessment visit for 
each site to collect samples for HLA typing according to their 
standard clinical practice (i.e. testing is to be performed 
locally and included as a pass-through cost in the study 
budget). This a safety provision for the unlikely event the 
autologous back-up product is not effective and allogeneic 
transplant is required. 
Increased busulfan dose range gives flexibility to either 
continue or revert back to the busulfan dose used in Cohort 
2. The DSMB will recommend the starting dose. The MRC has 
the discretion to reduce the dose in response to observation 
within the cohort. 
Various changes throughout for consistency 
Section 6.3.3 
Modification to the 
definition ‘delayed 
hematopoietic 
recovery’ to extend 
the time frame from 
21 to 42 days post- 
infusion. 
Change in platelet limit 
in definition of delayed 
hematopoietic 
recovery and bone 
marrow failure. 
Grade 4 neutropenia and grade 3 or 4 thrombocytopenia has 
been observed in the first 3 subjects of Cohort 2. The nadir 
for all 3  has occurred at Day 18 post –infusion. Originally it 
was anticipated that the nadir would occur approximately 9 
days post-infusion. As this nadir is occurring much later than 
anticipated, the timeline for definition of delayed 
hematopoietic recovery correspondingly needs adjustment. 
The platelet limit is increased from 20x103/μL to 25x103/μL, 
in line with the DAIDS grading scale for grade 4 
thrombocytopenia. Various changes throughout for 
consistency 
Section 6.3.5 
Removed reference to 
US Guidelines for the 
Use of Antiretroviral 
Agents in HIV-1 
Infected Adults and 
Adolescents. 
Guidelines have changed, and no longer specify a threshold 
CD4+ T 
lymphocyte count for commencement of ART. 
CCI


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Protocol Section Nature of Change 
Rationale 
Section 7.1.6 & 
7.1.7 
Change to 2 x 15L 
apheresis collections 
on Days 4 and 5 of G-
CSF will be performed 
instead of the current 1 
x 20L apheresis on Day 
5. 
Include provision to 
collect 100ml 
autologous plasma on 
the first day of CD34 
apheresis. Additional 
blood tests 
during mobilization 
Added description 
of optimal 
apheresis 
conditions. 
Three of the eight CD34+ manufacturing runs to date (Cohorts 
1 & 
2) have yielded the desired 2x106 HSPCtn/kg dose. Multiple 
smaller 
volume apheresis collections are often performed clinically 
and is expected to result in a higher yield of CD34+ cells than 
the current single collection, which, along with the changes 
to the mobilization protocol, will improve the feasibility of 
achieving the required minimum HSPCtn dose. 
The additional plasma is required for overnight storage of the 
CD34+ cells from the first apheresis. 
Peripheral blood CD34+ counts added on days 3 and 4 of 
mobilization and additional biochemistry monitoring, 
including creatinine clearance, for improved efficacy and 
toxicity monitoring of the new mobilization protocol. 
Description added to clarify goal with apheresis collections 
to minimise both red cell and platelet contamination, to 
assist with manufacturing processes. 
Various changes throughout and in the Schedule of 
Events for consistency 
Section 7.2.1 
Manual 
differential 
specified 
To improve reliability of local laboratory results, specification 
for a manual differential added to the required STAT 
CBC/differential during the busulfan follow up period. 
Section 7.2.5 
Additional bone 
marrow and GALT 
biopsies 
Additional biopsies will improve the available data on 
engraftment and distribution of the transplanted Cal-1-
modified cell. Feedback from Investigator’s is that the biopsy 
procedures have been well tolerated. 
Bone marrow aspirate and GALT biopsies added to Weeks 24 
and 
48, as well as early discontinuation at the discretion of the 
Investigator. 
Various changes throughout, including Schedule of Events and 
Appendix V for consistency. 
Appendix II 
Update to list of 
prohibited 
medication 
Clarification around the use of systemic 
glucocorticisteriods and updates to listed biological 
immunomodulatory agents and immunostimulants. 
Appendix IV 
Updates to 
contraindicated 
medication and 
delivery specifications 
Clarification added around use of common analgesia 
which is contraindicated with busulfan administration, 
or during the busulfan recovery period. 
Removed specific gauge requirement for the IV 
administration set, allowing investigator discretion. 
CCI


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Protocol Section Nature of Change 
Rationale 
Overview of 
Study Design 
Changed description of 
Cohort 3 dosing to 
include 
second dose based on 
real-time 
pharmacokinetic-
guided dosing to 
reach targeted drug 
exposure (AUC). 
Recommendation of the DSMB at the June 24, 2015 data review 
meeting to utilize a targeted busulfan dosing strategy (target of 
8000 μMol/L*min based on PK) vs a fixed dose scheme at the 
6mg/kg level, as a reduced intensity regimen. 
Schedule of 
Events: Pre 
Infusion 
Pre busulfan assessment 
visit updated to reflect 
≤11 days 
Changed Cohort 3, 1st 
dose of busulfan to Day 
-4 from Day -3 
Added wording to 
clarify Day -4 busulfan 
administration is for 
Cohort 3 only and Day 
-2 busulfan dosing for 
Cohort 2 & 3 
Updated various 
superscript 
footnote numbers 
Footnote 9 – changed 
to clarify that at visits 
G-CSF 
3 and  G-CSF 4 & 
plerixafor and 
CD34+ Apheresis, need 
CBC  from Local Lab 
(in addition to 
Central Laboratory 
CBC) 
Updated to correct for error in previous protocol version and 
adjust for change to Day -4 for first dose on busulfan in Cohort 3. 
Intent remains unchanged to perform pre conditioning assessment 
within 7 days prior to schedule busulfan infusion. 
Allows for needed turn-around-time for real-time PK analysis of 1st 
day  (Day -4) busulfan dose in order to calculate targeted 2nd 
busulfan dose (Day -2). 
Change for clarity. 
Updated to correct for errors in previous protocol version.  
Clarification only, as local CBC needed for safety before proceeding 
to next day’s dose of G-CSF but Central Labs required for data 
capture purposes. 
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Protocol Section Nature of Change 
Rationale 
Schedule of 
Events: Post 
Infusion 
Update post busulfan 
monitoring schedule 
from every 2 days ±1 to 
every 3 
days ±1 days, for 6 
weeks. 
Weeks 12, 24, 48 visits- 
Changed visit window 
for study visit and 
associated BM Aspirate 
and GALT to 
±1 week. 
Adjusted window allowance for consistency across the 6-week 
intensive monitoring period to enhance site and subject adherence 
with the protocol. 
Logistical adjustment to better accommodate procedural 
specialists and study subject availability; enhancing protocol 
adherence while maintaining reasonable visit and procedural 
window periods. 
6.3.3, 7.1.8, 
Appendix 4 
Changed text to reflect 
that Cohort 3 receives 
two doses of Busulfex® 
over 3 days (Day -4 and 
Day -2) and how it will 
be accomplished with 
real- time, 
pharmacokinetic- 
guided AUC-targeted 
dosing. 
Recommendation of the DSMB from the June 24, 2015 data review 
meeting to utilize a targeted busulfan dosing strategy (target of 
8000 μMol/L*min based on PK of 1st day busulfan infusion) instead 
of a fixed dose scheme at the 6mg/kg. The AUC target of 8,000 
μMol/L*min is recommended by the DSMB as a reduced intensity 
myeloconditioning regimen derived from experience with busulfan in 
oncology patients. 
Updated reference to busulfan visits and dosing in Schedule of 
Events and throughout document as applicable. 
6.3.4 
Changed Post-busulfan 
infection prophylaxis 
with 
trimethoprim- 
sulfamethoxazole (TMP- 
SMX) to be 
administered based on 
CD4+ T cell count 
Due to potential myelosuppressive effects of trimethoprim- 
sulfamethoxazole (TMP-SMX), changed instructions for 
administration of TMP-SMX from default administration commencing 
with busulfan dosing, but rather be based on a subject’s risk for 
Pneumocystis pneumonia (if CD4+ T cell count falls below 200/ml). 
7.2.1 
Update 
post 
busulfan 
monitoring schedule 
from every 2 days ±1 to 
every 3 days ±1 days, for 
6 weeks. 
Adjusted window allowance for consistency across the 6-week 
intensive monitoring period to enhance site and subject adherence 
with the protocol. 
 
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Protocol Section Nature of Change 
Rationale 
7.2.5, Appendix 
V 
Weeks 12, 24, 48 visits- 
Changed visit windows 
for study visit and 
associated 
BM Aspirate and GALT 
to 
±1 week. 
Logistical adjustment to better accommodate 
procedural specialists and study subject availability; 
enhancing protocol adherence while maintaining 
reasonable visit and procedural 
window periods. 
Updated reference to window periods in Schedule of 
Events and throughout document as applicable. 
Administrative/Clerical Updates 
Contacts 
Update 
Integrated an earlier update to the study contacts (version 
7.1) into 
this protocol amendment. 
6.3.3 
Changed text to clarify 
that dose is to be based 
on subject’s weight at 
the pre-busulfan 
assessment visit. 
Change for clarity only. 
7.3 
Changed requirement 
for 
creatinine clearance to 
be estimated by the 
Cockcroft-Gault 
equation to now be 
The central lab already provides the value utilizing the MDRD 
equation. This formula does not require the subject’s weight 
to be taken at every visit and is sufficient for this study 
indication. 
Appendix 5 
Added wording to allow 
the autologous plasma 
collection amounts to 
be adjusted. 
Depending on the cell processing laboratory specifications, 
these 
amounts may need to be adjusted for each collection. 
6.3.3 




7.1.5, 7.1.8, 
7.1.9 
Update “Conditioning 
Assessment” to ”Pre- 
busulfan Assessment” 


Corrected lab listings to 
match Schedule of 
Events 
Changed to correct visit name. 




Updated to correct for errors in previous protocol version. 

CCI


Protocol No: CAL-USA-11  
Document status: Mock Tables, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 1 of 24 
 
CAL-USA-11: Mock Tables: Table of Contents 
 
Contents 
 
Table 1: Protocol Deviation – Summary ................................................................................................................................................................................................................................. 4 
Table 2.1 Protocol Deviation – Major Deviations Summary ................................................................................................................................................................................................... 5 
Table 2.2 Protocol Deviation – Minor Deviations Summary .................................................................................................................................................................................................. 6 
Table 3: Demographics and Baseline Information ................................................................................................................................................................................................................. 7 
Table 4: HIV-1 History ............................................................................................................................................................................................................................................................. 8 
Table 5: Manufacturing CD4+ – Cohorts 1 and 2 and 3 .......................................................................................................................................................................................................... 9 
Table 6: Manufacturing CD34 – Cohorts 1 and 2 and 3 ........................................................................................................................................................................................................ 10 
Table 7: Manufacturing Deviations ...................................................................................................................................................................................................................................... 11 
Table 8.1 Cell Dose (x10e8) at Day 0 vs. Marking/Expression Data ...................................................................................................................................................................................... 12 
Table 9.1: Busulfan AUC (uMol/min) vs. Marking/Expression Data ..................................................................................................................................................................................... 13 
Table 10.1: CD4+ Count (mm3) ............................................................................................................................................................................................................................................. 14 
Table 10.2: CD4+ Count (mm3) vs. Marking/Expression Data .............................................................................................................................................................................................. 15 
Table 10.3.1. Log10 HIV-1-RNA Roche Assay (copies/mL) ..................................................................................................................................................................................................... 17 
Table 10.3.2 HIV-1-RNA Abbot Assay (copies/mL) ............................................................................................................................................................................................................... 17 
Table 10.4.1  HIV-1-RNA Roche Assay (copies/mL) vs. Marking/Expression Data ............................................................................................................................................................... 17 
Table 10.4.2 HIV-1-RNA Abbot Assay (copies/mL) vs. Marking/Expression Data ................................................................................................................................................................ 17 
Table 11.1 ANC (103/uL) vs. Marking/Expression Data ........................................................................................................................................................................................................ 17 
Table 11.2 Platelets (103/uL) vs. Marking/Expression Data.................................................................................................................................................................................................. 17 
Table 12 Lymphocyte Development and Chronic Inflammation vs. Marking/Expression .................................................................................................................................................... 17 
Table 13.1: Adverse Events (Summary SOC, PT) .................................................................................................................................................................................................................. 18 
Table 13.2: Adverse Events by CTC grade (Severity) ............................................................................................................................................................................................................ 19 
Table 13.2: Adverse Events by CTC grade (Severity) (Continued) ........................................................................................................................................................................................ 20 
Table 13.3: Treatment Emergent Adverse Events by Relationship to Study Drug (Causality) ............................................................................................................................................. 21 
Table 13.3: Treatment Emergent Adverse Events by Relationship to Study Drug (Causality) ............................................................................................................................................. 22 
Table 13.4: Treatment Emergent Adverse Events by Relationship to Study Procedure (Causality) ..................................................................................................................................... 23 
Table 13.4: Adverse Events by Relationship to Study Procedure (Causality) ....................................................................................................................................................................... 24 
 
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Tables, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 2 of 24 
GENERAL COMMENTS 
 
x
Where a count is 0, the percentage will not be shown (e.g. 0(0.0%) will be displayed as 0) 
x
Unless otherwise states, parameters will be listed in alphabetical order 
x
Percentages will be presented to one decimal place 
x
The minimum and maximum values will be presented to the same number of decimal places as recorded in the electronic Case Report Form (eCRF) 
x
Mean, median, and SD will be presented to one more decimal place than the raw data 
x
Percentages will be rounded to one decimal place, with the denominator being the number of subjects in the relevant population with non-missing data, unless 
otherwise specified 
x
Change from Baseline: 
Change from Baseline will be calculated as: 
ܥ݄ܽ݊݃݁݂ݎ݋݉ܾܽݏ݈݁݅݊݁ൌ݊݁ݓݒ݈ܽݑ݁െܾܽݏ݈݁݅݊݁ݒ݈ܽݑ݁ 
x
Unscheduled visits will be excluded from summary tables 
x
Names and order of Treatment Groups 
x
Cohort 1 (No Busulfan) 
x
Cohort 2 (One Dose Busulfan) 
x
Cohort 3 (Two Dose Busulfan) 
x
All  
 
x
Names of visits 
x
Screening 1 
x
Screening 2 
x
CD4+ Apheresis 
x
G-CSF 1 
x
G-CSF 2 
x
G-CSF 3 
x
G-CSF 4 
x
G-CSF 5 + CD34+ Apheresis (For cohorts 1 and 2, CD34 apheresis visit is on the same day as G-CSF 5 (G-CSF 5 + CD34 apheresis). For cohort 3, there are 2 
CD34 aphereses: G-CSF 4 & plerixafor + CD34 apheresis & G-CSF 5 + CD34 apheresis) 
x
Pre-Busulfan 
x
Busulfan (Day -3) 
x
Busulfan (Day -2) 
x
Infusion (Day 0) 
x
Week 1 
x
Week 2 
x
Week 4 
x
Week 6 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Tables, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 3 of 24 
x
Week 8 
x
Week 12 
x
Week 16 
x
Week 20 
x
Week 24 
x
Week 32 
x
Week 40 
x
Week 48
x
Busulfan Follow-up Regimen 
x
Early Discontinuation 
x
Follow-up Extension 
x
Column widths and text-wrapping may be altered in final output to best present the data 
x
Footnotes may be added/amended if required 
 
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Tables, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 4 of 24 
Table 1: Protocol Deviation – Summary 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
n(%) 
Cohort 1 
(No Busulfan) 
(N=X) 
Cohort 2 
(One Dose Busulfan) 
(N=X) 
Cohort 3 
(Two Dose Busulfan) 
(N=X) 
ALL 
 
(N=X) 
Subjects with at least 1 deviation over all 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
Number of deviations 
X 
X 
X 
X 
 
 
 
 
 
Screening 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
Screening 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
CD4+ Apheresis 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
G-CSF Administration 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
CD34+ Apheresis 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
Busulfan Administration and PK 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
Baseline 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
Week 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
Week 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
Week 4 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
Week 6 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
Week 8 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
Week 12 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
Week 16 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
Week 20 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
Week 24 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
Week 32 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
Week 40 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
Week 48 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
Note: Percentage is based on all enrolled subjects. 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
Programming Note: This table will be generated from the non-compliance 
tracker, as provided by the Clin Ops Team. 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Tables, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 5 of 24 
Table 2.1 Protocol Deviation – Major Deviations Summary  
Protocol: CAL-USA-11 
 
 
Clinical data cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM 
  
 
Programming Note: This table will be prepared by Callimmune. 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Tables, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 6 of 24 
Table 2.2 Protocol Deviation – Minor Deviations Summary  
Protocol: CAL-USA-11 
 
 
Clinical data cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM 
  
 
Programming Note: This table will be prepared by Callimmune. 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Tables, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 7 of 24 
Table 3: Demographics and Baseline Information 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
n(%) 
 
Cohort 1 
(No Busulfan) 
(N=X) 
Cohort 2 
(One Dose Busulfan) 
(N=X) 
Cohort 3 
(Two Dose Busulfan) 
(N=X) 
ALL 
 
(N=X) 
 
Age (years)* 
 
n 
X 
X 
X 
X 
 
Mean 
X.X 
X.X 
X.X 
X.X 
 
Median 
X.X 
X.X 
X.X 
X.X 
 
SD 
X.X 
X.X 
X.X 
X.X 
 
Min 
X 
X 
X 
X 
 
Max 
X 
X 
X 
X 
 
 
 
 
 
 
 
Gender (n%) 
 
Female 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
Male 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
Race n(%) 
 
Asian 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
Black 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
White 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
………… 
………… 
………… 
………… 
………… 
 
Ethnicity n(%) 
 
Hispanic/Latino 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
Non-Hispanic/Latino 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
*Age calculated at date of informed consent: = Integer(Date at informed consent – date of birth +1)/365.25) 
SD: Standard Deviation 
 
Clinical data cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM 
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Tables, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 8 of 24 
Table 4: HIV-1 History 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
 
 
Cohort 1 
(No Busulfan) 
(N=X) 
Cohort 2 
(One Dose Busulfan) 
(N=X) 
Cohort 3 
(Two Dose Busulfan) 
(N=X) 
ALL 
 
(N=X) 
 
Lowest CD4+ T Lymphocyte Count (cells/μl) 
 
n 
X 
X 
X 
X 
 
Mean 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
 
Median 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
 
SD 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
 
Min 
XXX 
XXX 
XXX 
XXX 
 
Max 
XXX 
XXX 
XXX 
XXX 
 
Highest Plasma HIV-1 Viral Load (copies/mL) 
 
n 
X 
X 
X 
X 
 
Mean 
XXX,XXX.X 
XXX,XXX.X 
XXX,XXX.X 
XXX,XXX.X 
 
Median 
XXX,XXX.X 
XXX,XXX.X 
XXX,XXX.X 
XXX,XXX.X 
 
SD 
XXX,XXX.X 
XXX,XXX.X 
XXX,XXX.X 
XXX,XXX.X 
 
Min 
XXX,XXX 
XXX,XXX 
XXX,XXX 
XXX,XXX 
 
Max 
XXX,XXX 
XXX,XXX 
XXX,XXX 
XXX,XXX 
 
 
 
 
 
 
SD: Standard Deviation 
 
Clinical data cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM 
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Tables, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 9 of 24 
Table 5: Manufacturing CD4+ – Cohorts 1 and 2 and 3 
Protocol: CAL-USA-11 
Population: Safety 
 
Cohort: Cohort 1 (No Busulfan)  
 
6XEMHFW1XPEHU

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&'$SKHUHVLV
$SKHUHVLV9ROXPH/
[[[
[[[
[[[
[[[
7RWDOQXPEHURIFHOOVFROOHFWHG
[AFHOOV
[[[[
[[[[
[[[[
[[[[
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[[
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&'
[[[
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7RWDOQXPEHURI&'FHOOVFROOHFWHG
[A&'
[[[
[[[
[[[
[[[
&')LQDO&HOO3URGXFW7WQ
7RWDOYLDEOH&'FHOOV
$WWKHHQGRIWKHPDQXIDFWXULQJSURFHVV
[AFHOOV
[[[
[[[
[[[
[[[
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[[[
[[[
[[[
[[[
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[[[
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7UDQVGXFWLRQ(IILFLHQF\
GHWHUPLQHGE\)$&6
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[[[
7UDQVGXFWLRQ(IILFLHQF\
GHWHUPLQHGE\:35(T3&5YHFWRUFHOO
[[[
[[[
[[[
[[[
(VWLPDWHG7WQ'RVH
EDVHGRQ%RG\:HLJKWDW$SKHUHVLVYLVLW[AFHOOVNJ
[[[
[[[
[[[
[[[
,QIXVLRQ%DVHOLQH
%RG\:HLJKW
DW%DVHOLQHYLVLWNJ
[[[[
[[[[
[[[[
[[[[
$FWXDO7WQ'RVH
EDVHGRQ%RG\:HLJKWRQWKH'D\RI,QIXVLRQ
[AFHOOVNJ
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Clinical data cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM 
 
Programming Note: Create this table for all cohorts. 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Tables, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 10 of 24 
Table 6: Manufacturing CD34 – Cohorts 1 and 2 and 3 
Protocol: CAL-USA-11 
Population: Safety 
 
Cohort: Cohort 1 (No Busulfan)  
 
6XEMHFW1XPEHU

[[[[[[[
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[[[[[[[

[[[[[[[
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&'$SKHUHVLV
$SKHUHVLV9ROXPH/
[[[
[[[
[[[
[[[
7RWDOQXPEHURIFHOOVFROOHFWHG
[AFHOOV
[[[[
[[[[
[[[[
[[[[
$JHRI6XEMHFW
DW$SKHUHVLVYLVLW\UV
[[
[[
[[
[[
RI&'LQWKHFROOHFWHGFHOOV
&'
[[[
[[[
[[[
[[[
7RWDOQXPEHURI&'FHOOVFROOHFWHG
[A&'
[[[
[[[
[[[
[[[
&')LQDO&HOO3URGXFW+63&WQ
7RWDOYLDEOH&'FHOOV
$WWKHHQGRIWKHPDQXIDFWXULQJSURFHVV
[AFHOOV
[[[
[[[
[[[
[[[
3XULW\&'
[[[
[[[
[[[
[[[
9LDELOLW\
[[[
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7UDQVGXFWLRQ(IILFLHQF\
GHWHUPLQHGE\)$&6
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[[[
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DW%DVHOLQHYLVLWNJ
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Clinical data cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
Programming Note: Create this table for all cohorts. 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Tables, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 11 of 24 
Table 7: Manufacturing Deviations 
Protocol: CAL-USA-11 
Population: Safety 
 
 
Clinical data cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM 
 
 
Programming Note: This table will be prepared by Callimmune. 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Tables, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 12 of 24 
Table 8.1 Cell Dose (x10e8) at Day 0 vs. Marking/Expression Data  
Protocol: CAL-USA-11 
Population: Safety 
 
Parameters: Peripheral Blood 
Marking/Expression: Cal-1 Marking (WPRE qPCR) (%) 
Subject Number 
Cohort 1 
(No Busulfan) 
(N=X) 
Cell Dose at Day 0 (x10e8) 
Cal-1 Marking (WPRE qPCR) (%) 
Ttn (CD4+) Dose  
HSPCtn (CD34+) Dose 
Peak 
Week 48 
 
 
 
 
 
[[[[[[[ 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
[[[[[[[ 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
[[[[[[[ 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
[[[[[[[ 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
 
 
 
 
 
n 
X 
X 
X 
X 
Mean 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
Median 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
SD 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
Min 
XXX 
XXX 
XXX 
XXX 
Max 
XXX 
XXX 
XXX 
XXX 
 
 
 
 
 
Cell Dose (x10e8) vs. Peak Cal-1 Marking (WPRE qPCR) (%) 
 
 
 
 
    Pearson product-moment correlation 
x.xxx 
x.xxx 
 
 
    Spearman correlation coefficient 
x.xxx 
x.xxx 
 
 
 
 
 
 
 
Cell Dose (x10e8) vs. Week 48 Cal-1 Marking (WPRE qPCR) (%) 
 
 
 
 
    Pearson product-moment correlation 
x.xxx 
x.xxx 
 
 
    Spearman correlation coefficient 
x.xxx 
x.xxx 
 
 
 
 
 
 
 
SD: Standard Deviation; “Not Detectable” Cal-Marking WPRE qPCR) (%) is set to 0. 
 
Subject XX-XXXXX: Peak Cal-1 Marking (WPRE qPCR) (%) collected at Week X. Latest time point used as Week 48: Week X. 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
Programming Note: Repeat this table for all cohorts and overall.  
This table will also be repeated (below)for all parameters (Peripheral Blood, Peripheral Blood 
Subsets: monocytes, granulocytes, CD8+ lymphocytes, CD4+ lymphocytes, Bone Marrow and GALT 
(both locations) and all markings/expression (Cal-1 Marking (WPRE qPCR) (copies/cell), 
Cal-1 C46 Expression (C46 RTqPCR) (relative expression), Cal-1 sh5 Expression (sh5 RTqPCR) (relative 
expression)). 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Tables, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 13 of 24 
Table 9.1: Busulfan AUC (uMol/min) vs. Marking/Expression Data  
Protocol: CAL-USA-11 
Population: Safety 
 
Parameters: Peripheral Blood 
Marking/Expression: Cal-1 Marking (WPRE qPCR) (%) 
Subject Number 
Cohort 2 
(One Dose Busulfan) 
(N=X) 
Busulfan AUC 
(uMol/min) 
at Day -4 
Busulfan AUC 
(uMol/min) 
at Day -2 
Total Busulfan 
AUC (uMol/min) 
(Day -4 + Day -2) 
Cal-1 Marking (WPRE qPCR) (%) 
Peak  
Week 48 
 
 
 
 
 
 
[[[[[[[ 
N/A 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
[[[[[[[ 
 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
[[[[[[[ 
 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
[[[[[[[ 
 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
 
 
 
 
 
 
n 
 
X 
X 
X 
X 
Mean 
 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
Median 
 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
SD 
 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
Min 
 
XXX 
XXX 
XXX 
XXX 
Max 
 
XXX 
XXX 
XXX 
XXX 
 
 
 
 
 
 
Busulfan AUC (uMol/min)at Day -2 vs. Peak Cal-1 Marking (WPRE qPCR) (%) 
 
 
 
 
 
    Pearson product-moment correlation 
 
x.xxx 
x.xxx 
 
 
    Spearman correlation coefficient 
 
x.xxx 
x.xxx 
 
 
 
 
 
 
 
 
Busulfan AUC (uMol/min)at Day -2 vs. Week 48 Cal-1 Marking (WPRE qPCR) (%) 
 
 
 
 
 
    Pearson product-moment correlation 
 
x.xxx 
x.xxx 
 
 
    Spearman correlation coefficient 
 
x.xxx 
x.xxx 
 
 
 
 
 
 
 
 
 
SD: Standard Deviation; “Not Detectable” Cal-Marking WPRE qPCR) (%) is set to 0. 
 
Subject XX-XXXXX: Peak Cal-1 Marking (WPRE qPCR) (%) collected at Week X. Latest time point used as Week 48: Week X. 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
Programming Note:  
This table will be repeated (below) for all parameters (Peripheral Blood, Peripheral Blood Subsets: monocytes, granulocytes, CD8+ 
lymphocytes, CD4+ lymphocytes, Bone Marrow and GALT (both locations) and all markings/expression (Cal-1 Marking (WPRE qPCR) 
(copies/cell), Cal-1 C46 Expression (C46 RTqPCR) (relative expression), Cal-1 sh5 Expression (sh5 RTqPCR) (relative expression)). 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Tables, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 14 of 24 
Table 10.1: CD4+ Count (mm3) 
Protocol: CAL-USA-11 
Population: Safety 
 
Subject Number 
Cohort 1 
(No Busulfan) 
(N=X) 
 
Baseline CD4+ Count (mm3) 
Maximum CD4+ Count (mm3) post the start of the 
transduced cell infusion 
Week 48 CD4+ Count (mm3) 
 
Screening  
Pre-
Apheresis 
Pre-
Infusion 
Actual 
Value 
Change from 
Screening 
Change from 
Pre-Apheresis 
Change from 
Pre-Infusion 
Actual 
Value 
Change from 
Screening 
Change from 
Pre-Apheresis 
Change from 
Pre-Infusion 
 
 
 
 
 
 
 
 
 
 
 
 
[[[[[[[ 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
[[[[[[[ 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
[[[[[[[ 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
[[[[[[[ 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
 
 
 
 
 
 
 
 
 
 
 
 
n 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Mean 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
Median 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
SD 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
Min 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
Max 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
 
 
 
 
 
 
 
 
 
 
 
 
H0: Change = 0 
 
 
 
 
 
 
 
 
 
 
 
  95% CI for the Mean 
 
 
 
 
(XX.XX, XX.XX) (XX.XX, XX.XX) (XX.XX, XX.XX) 
 
(XX.XX, XX.XX) (XX.XX, XX.XX) 
(XX.XX, XX.XX) 
  P-value (Student t)- 
 
 
 
 
X.XXXX 
X.XXXX 
X.XXXX 
 
X.XXXX 
X.XXXX 
X.XXXX 
 
 
 
 
 
 
 
 
 
 
 
 
  95% CI for the Median 
 
 
 
 
(XX.XX, XX.XX) (XX.XX, XX.XX) (XX.XX, XX.XX) 
 
(XX.XX, XX.XX) (XX.XX, XX.XX) 
(XX.XX, XX.XX) 
  P-value (Signed Rank)- 
 
 
 
 
X.XXXX 
X.XXXX 
X.XXXX 
 
X.XXXX 
X.XXXX 
X.XXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SD: Standard Deviation 
CD4+ Count (mm3) at Screening = Average of Screening 1 and Screening 2 values 
CI: Confidence Interval 
 
Subject XX-XXXXX: Maximum value post the start of the transduced cell infusion collected at Week X. Latest time point used as Week 48: Week X. 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
CCI


Protocol No: CAL-USA-11  
Document status: Mock Tables, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 15 of 24 
 
Table 10.2: CD4+ Count (mm3) vs. Marking/Expression Data  
Protocol: CAL-USA-11 
Population: Safety 
 
Parameters: Peripheral Blood 
Marking/Expression: Cal-1 Marking (WPRE qPCR) (%) 
 
Subject Number 
Cohort 1 
(No Busulfan) 
(N=X) 
 
CD4+ Count (mm3) 
Cal-1 Marking 
(WPRE qPCR) (%) 
 
Baseline 
Maximum value post the start of the 
transduced cell infusion 
Week 48 
 
Screening 
Pre-
Apheresis 
Pre-
Infusion 
Actual 
Value 
Change 
from 
Screening 
Change 
from Pre-
Apheresis 
Change 
from Pre-
Infusion 
Actual 
Value 
Change 
from 
Screening 
Change 
from Pre-
Apheresis 
Change 
from Pre-
Infusion 
Peak 
Week 48 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[[[[[[[ 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
[[[[[[[ 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
[[[[[[[ 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
n 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Mean 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
Median 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
SD 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
XXX.X 
Min 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
Max 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CD4+ Count (mm3) vs. Peak Cal-1 
Marking (WPRE qPCR) (%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
    Pearson product-moment correlation 
x.xxx 
x.xxx 
x.xxx 
 
x.xxx 
x.xxx 
x.xxx 
 
x.xxx 
x.xxx 
x.xxx 
 
 
    Spearman correlation coefficient 
x.xxx 
x.xxx 
x.xxx 
 
x.xxx 
x.xxx 
x.xxx 
 
x.xxx 
x.xxx 
x.xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CD4+ Count (mm3) vs. Week 28 Cal-1 
Marking (WPRE qPCR) (%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
    Pearson product-moment correlation 
x.xxx 
x.xxx 
x.xxx 
 
x.xxx 
x.xxx 
x.xxx 
 
x.xxx 
x.xxx 
x.xxx 
 
 
    Spearman correlation coefficient 
x.xxx 
x.xxx 
x.xxx 
 
x.xxx 
x.xxx 
x.xxx 
 
x.xxx 
x.xxx 
x.xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Tables, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 16 of 24 
SD: Standard Deviation; “Not Detectable” Cal-Marking WPRE qPCR) (%) is set to 0. 
CD4+ Count (mm3) at Screening = Average of Screening 1 and Screening 2 values 
 
Subject XX-XXXXX: Maximum CD4+ Count (mm3) value post the start of the transduced cell infusion collected at Week X. Latest time point used as Week 48: Week X. 
 
Peak Cal-1 Marking (WPRE qPCR) (%) collected at Week X. Latest time point used as Week 48: Week X. 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
Programming Note: Repeat this table for all applicable cohorts and 
overall. 
This table will also be repeated (below) for all parameters (Peripheral 
Blood, Peripheral Blood Subsets: monocytes, granulocytes, CD8+ 
lymphocytes, CD4+ lymphocytes, Bone Marrow and GALT (both locations) 
and all markings/expression (Cal-1 Marking (WPRE qPCR) (copies/cell), 
Cal-1 C46 Expression (C46 RTqPCR) (relative expression), Cal-1 sh5 
Expression (sh5 RTqPCR) (relative expression)). 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Tables, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 17 of 24 
Table 10.3.1. Log10 HIV-1-RNA Roche Assay (copies/mL) 
Repeat Table 10.1, but include minimum Log10 HIV-1-RNA Roche Assay value post the start of the transduced cell infusion, not maximum Log10 HIV-1-RNA Roche 
Assay value. 
 
Table 10.3.2 HIV-1-RNA Abbot Assay (copies/mL) 
Repeat Table 10.1, but include minimum Log10 HIV-1-RNA Roche Assay value post the start of the transduced cell infusion, not maximum Log10 HIV-1-RNA Abbot 
Assay value. 
 
Table 10.4.1  HIV-1-RNA Roche Assay (copies/mL) vs. Marking/Expression Data 
Repeat Table 10.2, but include minimum Log10 HIV-1-RNA Roche Assay value post the start of the transduced cell infusion, not maximum Log10 HIV-1-RNA Roche 
Assay value. 
 
Table 10.4.2 HIV-1-RNA Abbot Assay (copies/mL) vs. Marking/Expression Data 
Repeat Table 10.2, but include minimum Log10 HIV-1-RNA Roche Assay value post the start of the transduced cell infusion, not maximum Log10 HIV-1-RNA Abbot 
Assay value. 
 
Table 11.1 ANC (103/uL) vs. Marking/Expression Data 
Repeat Table 10.2, but include minimum ANC value post the start of the transduced cell infusion, not maximum ANC value. 
 
Table 11.2 Platelets (103/uL) vs. Marking/Expression Data 
Repeat Table 10.2, but include minimum Platelet value post the start of the transduced cell infusion, not maximum Platelet value. 
 
Table 12 Lymphocyte Development and Chronic Inflammation vs. Marking/Expression 
Repeat Table 10.2 for Lymphocyte Development and Chronic Inflammation parameters 
 
 
 
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Tables, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 18 of 24 
Table 13.1: Adverse Events (Summary SOC, PT) 
Protocol: CAL-USA-11 
Population: Safety 
 
System Organ Class 
            Preferred Term 
Cohort 1 
(No Busulfan) 
(N=X) 
 
Cohort 2 
(One Dose Busulfan) 
(N=X) 
 
Cohort 3 
(Two Dose Busulfan) 
(N=X) 
 
ALL 
 
(N=X) 
Subjects 
AEs 
 
Subjects 
AEs 
 
Subjects 
AEs 
 
Subjects 
AEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
All Body Systems 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
0 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
SOC1 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT1 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT2 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
…. 
…. 
…. 
 
…. 
…. 
 
…. 
…. 
 
…. 
…. 
 
PTx 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
SOC2 
X (XX.X%) 
X 
 
0 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT1 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
PT2 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
…. 
…. 
…. 
 
…. 
…. 
 
…. 
…. 
 
…. 
…. 
 
PTx 
0 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
 
X (XX.X%) 
X 
……….. 
 
 
 
 
 
 
 
 
 
 
 
AE: Adverse Events 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Tables, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 19 of 24 
Table 13.2: Adverse Events by CTC grade (Severity) 
Protocol: CAL-USA-11 
Population: Safety 
 
System Organ Class (SOC) 
         Preferred Term (PT) 
 
Cohort 1 
(No Busulfan) 
(N=X) 
Cohort 2 
(One Dose Busulfan) 
(N=X) 
 
Mild 
(Grade 1) 
Moderate 
 (Grade 2) 
Severe  
(Grade 3) 
Potentially 
Life-
Threatening 
(Grade 4) 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe  
(Grade 3) 
Potentially 
 Life-
Threatening 
(Grade 4) 
 
 
 
 
 
 
 
 
 
 
All Body Systems 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
SOC1 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PT1 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PT2 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           …. 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PTx 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
SOC2 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PT1 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PT2 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           …. 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PTx 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
Note: Subjects are counted once at maximum severity within each sub grouping  
Note: Percentages are based on the number of subjects in each group 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Tables, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 20 of 24 
Table 13.2: Adverse Events by CTC grade (Severity) (Continued) 
Protocol: CAL-USA-11 
Population: Safety 
 
System Organ Class (SOC) 
         Preferred Term (PT) 
 
Cohort 3 
(Two Dose Busulfan) 
(N=X) 
ALL 
 
(N=X) 
 
Mild 
(Grade 1) 
Moderate 
 (Grade 2) 
Severe  
(Grade 3) 
Potentially 
Life-
Threatening 
(Grade 4) 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe  
(Grade 3) 
Potentially 
 Life-
Threatening 
(Grade 4) 
 
 
 
 
 
 
 
 
 
 
All Body Systems 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
SOC1 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PT1 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PT2 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           …. 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PTx 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
SOC2 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PT1 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PT2 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           …. 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PTx 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
Note: Subjects are counted once at maximum severity within each sub grouping  
Note: Percentages are based on the number of subjects in each group 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Tables, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 21 of 24 
Table 13.3: Treatment Emergent Adverse Events by Relationship to Study Drug (Causality) 
Protocol: CAL-USA-11 
Population: Safety 
 
System Organ Class (SOC) 
           Preferred Term (PT) 
 
Cohort 1 
(No Busulfan) 
(N=X) 
Cohort 2 
(One Dose Busulfan) 
(N=X) 
 
Not 
Related 
Doubtful  
Possible 
Probable 
Very Likely 
Not 
Related 
Doubtful 
Possible 
Probable 
Very Likely 
 
 
 
 
 
 
 
 
 
 
 
 
All Body Systems 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
 
 
SOC1 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PT1 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PT2 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           …. 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PTx 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
 
 
SOC2 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PT1 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PT2 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           …. 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PTx 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Subjects are counted once at maximum relatedness within each sub grouping  
Note: Percentages are based on the number of subjects in each group 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Tables, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 22 of 24 
Table 13.3: Treatment Emergent Adverse Events by Relationship to Study Drug (Causality) 
Protocol: CAL-USA-11 
Population: Safety 
 
System Organ Class (SOC) 
           Preferred Term (PT) 
 
Cohort 3 
(Two Dose Busulfan) 
(N=X) 
ALL 
 
(N=X) 
 
Not 
Related 
Doubtful  
Possible 
Probable 
Very Likely 
Not 
Related 
Doubtful 
Possible 
Probable 
Very Likely 
 
 
 
 
 
 
 
 
 
 
 
 
All Body Systems 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
 
 
SOC1 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PT1 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PT2 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           …. 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PTx 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
 
 
SOC2 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PT1 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PT2 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           …. 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PTx 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Subjects are counted once at maximum relatedness within each sub grouping  
Note: Percentages are based on the number of subjects in each group 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Tables, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 23 of 24 
Table 13.4: Treatment Emergent Adverse Events by Relationship to Study Procedure (Causality) 
Protocol: CAL-USA-11 
Population: Safety 
 
Study Procedure: Busulfan 
 
System Organ Class (SOC) 
           Preferred Term (PT) 
 
Cohort 1 
(No Busulfan) 
(N=X) 
Cohort 2 
(One Dose Busulfan) 
(N=X) 
 
Not 
Related 
Doubtful  
Possible 
Probable 
Very Likely 
Not 
Related 
Doubtful 
Possible 
Probable 
Very Likely 
 
 
 
 
 
 
 
 
 
 
 
 
All Body Systems 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
 
 
SOC1 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PT1 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PT2 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           …. 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PTx 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
 
 
SOC2 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PT1 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PT2 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           …. 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PTx 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Subjects are counted once at maximum relatedness within each sub grouping  
Note: Percentages are based on the number of subjects in each group 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
Programming Note: Repeat for all study procedures: GCSF, : Bone 
Marrow Aspiration, etc. 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Tables, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 24 of 24 
Table 13.4: Adverse Events by Relationship to Study Procedure (Causality) 
Protocol: CAL-USA-11 
Population: Safety 
 
Study Procedure: Busulfan 
 
System Organ Class (SOC) 
           Preferred Term (PT) 
 
Cohort 3 
(Two Dose Busulfan) 
(N=X) 
ALL 
 
(N=X) 
 
Not 
Related 
Doubtful  
Possible 
Probable 
Very Likely 
Not 
Related 
Doubtful 
Possible 
Probable 
Very Likely 
 
 
 
 
 
 
 
 
 
 
 
 
All Body Systems 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
 
 
SOC1 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PT1 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PT2 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           …. 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PTx 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
 
 
SOC2 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PT1 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PT2 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           …. 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
           PTx 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Subjects are counted once at maximum relatedness within each sub grouping  
Note: Percentages are based on the number of subjects in each group 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
Programming Note: Repeat for all study procedures: GCSF, : Bone 
Marrow Aspiration, etc. 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 1 of 59 
 
CAL-USA-11: Mock Listings: Table of Contents 
 
Contents 
 
Listing 1.1: Subject Disposition ............................................................................................................................................................................................................................................... 5 
Listing 1.2: Subject Disposition (continued) ........................................................................................................................................................................................................................... 6 
Listing 2: Subject Withdrawal ................................................................................................................................................................................................................................................. 7 
Listing 3: Subject Discontinuation .......................................................................................................................................................................................................................................... 8 
Listing 4.1: Demographics ...................................................................................................................................................................................................................................................... 9 
Listing 4.2: Pre-Busulfan Body Weight ................................................................................................................................................................................................................................. 10 
Listing 5: HIV-1 History ......................................................................................................................................................................................................................................................... 11 
Listing 6: Medical History ..................................................................................................................................................................................................................................................... 12 
Listing 7: Eligibility ................................................................................................................................................................................................................................................................ 13 
Listing 8.1: Pregnancy Test ................................................................................................................................................................................................................................................... 14 
Listing 8.2: Positive Pregnancy Test ..................................................................................................................................................................................................................................... 15 
Listing 9: Chest X-Rays .......................................................................................................................................................................................................................................................... 16 
Listing 10: ART Therapy History (regimen overview) ........................................................................................................................................................................................................... 17 
Listing 11: Transduced CD4+ Cell Product Dose (Transduction efficiency, viability, cell numbers for Ttn) ........................................................................................................................... 18 
Listing 12: Transduced CD34+ Cell Product Dose (Transduction efficiency, viability, cell numbers for HSPCtn) .................................................................................................................. 19 
Listing 13.1: G-CSF Therapy .................................................................................................................................................................................................................................................. 20 
Listing 13.2: Plerixafor Therapy ............................................................................................................................................................................................................................................ 21 
Listing 14.1: Apheresis - CD4+ .............................................................................................................................................................................................................................................. 22 
Listing 14.2: Apheresis - CD34+ ............................................................................................................................................................................................................................................ 23 
Listing 15.1: Busulfan Dosing ................................................................................................................................................................................................................................................ 24 
Listing 15.1: Busulfan Interruptions ..................................................................................................................................................................................................................................... 25 
Listing 15.3: Busulfan Administration and Pharmacokinetics .............................................................................................................................................................................................. 26 
Listing 16: Cal-1 Marking/Expression - Peripheral Blood ..................................................................................................................................................................................................... 27 
Listing 17: Cal-1 Marking/Expression – Bone Marrow ......................................................................................................................................................................................................... 28 
Listing 18: Cal-1 Marking/Expression – GALT ....................................................................................................................................................................................................................... 29 
Listing 19.1: Cal-1 Marking/Expression – Subsets Monocytes ............................................................................................................................................................................................. 30 
Listing 19.2: Cal-1 Marking/Expression – Subsets: Granulocytes ......................................................................................................................................................................................... 31 
Listing 19.3: Cal-1 Marking/Expression – Subsets: CD4+ Lymphocytes ................................................................................................................................................................................ 32 
Listing 19.4: Cal-1 Marking/Expression – Subsets: CD8+ Lymphocytes ................................................................................................................................................................................ 33 
Listing 20.1: Serious Adverse Events, including event narratives......................................................................................................................................................................................... 34 
Listing 20.2: Deaths .............................................................................................................................................................................................................................................................. 35 
Listing 21.1: Adverse Events (All Grades) ............................................................................................................................................................................................................................. 36 
Listing 21.2: Adverse Events (Grades 3 and /or 4) ............................................................................................................................................................................................................... 37 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 2 of 59 
Listing 21.3: Related Adverse Events (Grades 3 and /or 4) .................................................................................................................................................................................................. 38 
Listing 22.1: Concomitant Medication ................................................................................................................................................................................................................................. 39 
Listing 22.2: Concomitant Procedures and Therapies .......................................................................................................................................................................................................... 40 
Listing 23.1: Laboratory – Hematology ................................................................................................................................................................................................................................ 41 
Listing 23.2: Laboratory – Hematology (Abnormal only)...................................................................................................................................................................................................... 42 
Listing 24.1: Laboratory – Biochemistry ............................................................................................................................................................................................................................... 43 
Listing 24.2: Biochemistry (Abnormal only) ......................................................................................................................................................................................................................... 44 
Listing 25.1: Lymphocyte phenotype ................................................................................................................................................................................................................................... 45 
Listing 25.2: Thymopoieisis .................................................................................................................................................................................................................................................. 46 
Listing 25.3: Inflammation .................................................................................................................................................................................................................................................... 47 
Listing 25.4: Maturation ....................................................................................................................................................................................................................................................... 48 
Listing 26: Laboratory – HIV-1 RNA ...................................................................................................................................................................................................................................... 49 
Listing 27.1: Vital Signs ......................................................................................................................................................................................................................................................... 50 
Listing 27.2: Abnormal Vital Signs ........................................................................................................................................................................................................................................ 51 
Listing 28.1: Physical Examination ........................................................................................................................................................................................................................................ 52 
Listing 28.2: Abnormal: Physical Examination ...................................................................................................................................................................................................................... 53 
Listing 29.1: Cal-1 Integration Analysis................................................................................................................................................................................................................................. 54 
Listing 29.2: Cal-1 Integration Analysis (Re-test) .................................................................................................................................................................................................................. 55 
Listing 30: Replication Competent Lentivirus (RCL) .............................................................................................................................................................................................................. 56 
Listing 31: HIV-1 Tropism Assay ........................................................................................................................................................................................................................................... 57 
Listing 32.1: C46 Immunogenicity – Humoral Response ...................................................................................................................................................................................................... 58 
Listing 32.2: C46 Immunogenicity – Cellular Response ........................................................................................................................................................................................................ 59 
 
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 3 of 59 
GENERAL COMMENTS 
 
x
Names and order of Treatment Groups 
x
Cohort 1 (No Busulfan) 
x
Cohort 2 (One Dose Busulfan) 
x
Cohort 3 (Two Dose Busulfan) 
x
All  
 
x
Names of visits 
x
Screening 1 
x
Screening 2 
x
CD4+ Apheresis 
x
G-CSF 1 
x
G-CSF 2 
x
G-CSF 3 
x
G-CSF 4 
x
G-CSF 5 + CD34+ Apheresis (For cohorts 1 and 2, CD34 apheresis visit is on the same day as G-CSF 5 (G-CSF 5 + CD34 apheresis). For cohort 3, there are 2 
CD34 aphereses: G-CSF 4 & plerixafor + CD34 apheresis & G-CSF 5 + CD34 apheresis) 
x
Pre-Busulfan 
x
Busulfan (Day -3) 
x
Busulfan (Day -2) 
x
Infusion (Day 0) 
x
Week 1 
x
Week 2 
x
Week 4 
x
Week 6 
x
Week 8 
x
Week 12 
x
Week 16 
x
Week 20 
x
Week 24 
x
Week 32 
x
Week 40 
x
Week 48
x
Busulfan Follow-up Regimen 
x
Early Discontinuation 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 4 of 59 
x
Follow-up Extension 
x
Column widths and text-wrapping may be altered in final output to best present the data 
x
Footnotes may be added/amended if required 
 
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 5 of 59 
Listing 1.1: Subject Disposition 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
Subject 
Number 
Informed 
Consent Date 
(YYYY-MM-DD) 
CD34+ 
Apheresis Date 
(YYYY-MM-DD) 
Infusion Date 
(YYYY-MM-DD) 
Enrolled Population 
Safety Population 
xx-xxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
YYYY-MM-DD 
Yes 
No 
xx-xxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
YYYY-MM-DD 
Yes 
No 
xx-xxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
YYYY-MM-DD 
Yes 
Yes 
xx-xxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
YYYY-MM-DD 
Yes 
Yes 
 
 
 
 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 6 of 59 
Listing 1.2: Subject Disposition (continued) 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
Subject 
Number 
CD4+ 
Apheresis Date 
(YYYY-MM-DD) 
Status (Ongoing, 
Discontinuation, 
Withdrawal or 
Completion)1 
Date of 
Discontinuation, 
Withdrawal or 
Completion 
(YYYY-MM-DD) 
Date Antiretroviral 
Therapy 
Commenced 
Time from CD4+ 
Apheresis to 
Commencement of ART 
(days)3 
Last Visit 
Prior to 
Discontinuation 
or Withdrawal 
Last 
Scheduled 
Visit 
Primary Reason for 
Discontinuation or 
Withdrawal2 
 
 
 
 
 
 
 
 
xx-xxxxxx 
YYYY-MM-DD 
Discontinuation 
YYYY-MM-DD 
YYYY-MM-DD 
xx 
Week xx 
Week xx 
Commencement of 
antiretroviral therapy 
xx-xxxxxx 
YYYY-MM-DD 
Discontinuation 
YYYY-MM-DD 
 
xx 
Week xx 
Week xx 
Commencement of 
antiretroviral therapy 
xx-xxxxxx 
YYYY-MM-DD 
Completed 
YYYY-MM-DD 
 
xx 
- 
Week xx 
 
xx-xxxxxx 
YYYY-MM-DD 
Completed 
YYYY-MM-DD 
 
xx 
- 
Week xx 
 
 
 
 
 
 
 
 
 
1 Withdrawal: any subject who withdrew consent from the trial; Discontinuation: any subject who discontinued from primary endpoint analysis 
2 Last scheduled visit before discontinuation or withdrawal. 
3 Date Antiretroviral Therapy Commenced / Date of Discontinuation, Withdrawal or Completion - CD4+ Apheresis Date + 1 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
Programming Note: Include all detail with regards to reason for 
discontinuation in “Primary Reason for Discontinuation or Withdrawal2”: 
x
SAE number if applicable 
x
AE number if applicable 
x
Manufacturing failure details if applicable 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 7 of 59 
Listing 2: Subject Withdrawal 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
Subject Number 
Date of Withdrawal 
(YYYY-MM-DD) 
Phase of 
Withdrawal1 
Primary Reason for Withdrawal 
Secondary Reason for Withdrawal * 
 
 
xx-xxxxxx 
YYYY-MM-DD 
Post-infusion phase 
Commencement of antiretroviral therapy Other: XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
xx-xxxxxx 
YYYY-MM-DD 
Post-infusion phase 
Commencement of antiretroviral therapy Other: XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
xx-xxxxxx 
YYYY-MM-DD 
Post-infusion phase 
Commencement of antiretroviral therapy Other: XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
 
 
* Withdrawal occurred in Post-Infusion phase. 
1 Withdrawal: any subject who withdrew consent from the trial 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 8 of 59 
Listing 3: Subject Discontinuation 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
Subject Number 
Date of 
Discontinuation 
(YYYY-MM-DD) 
Phase of 
Discontinuation 
Last Visit Prior to 
Discontinuation 
Primary Reason for Discontinuation 
 
 
 
 
xx-xxxxxx 
YYYY-MM-DD 
Post-infusion phase 
Week xx 
Commencement of antiretroviral therapy 
xx-xxxxxx 
YYYY-MM-DD 
Post-infusion phase 
Week xx 
Commencement of antiretroviral therapy 
xx-xxxxxx 
YYYY-MM-DD 
Post-infusion phase 
Week xx 
Commencement of antiretroviral therapy 
 
 
 
 
Note: Subject discontinuation refers to any subject who discontinued from the primary endpoint analysis 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 9 of 59 
Listing 4.1: Demographics 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
Subject 
Number 
Center 
Gender 
Date of Birth 
(YYYY-MM-DD) 
Age* 
Race 
Ethnicity 
Child Bearing Potential 
 
 
 
 
 
 
xx-xxxxxx 
Quest Clinical Research: Dr Lalezari 
Male 
YYYY-MM-DD 
xx 
White 
Not Hispanic or Not Latino 
 
xx-xxxxxx 
UCLA CARE Center Clinic: Dr 
Mitsuyasu 
Male 
YYYY-MM-DD 
xx 
White 
Not Hispanic or Not Latino 
 
xx-xxxxxx 
Quest Clinical Research: Dr Lalezari 
Female 
YYYY-MM-DD 
xx 
White 
Not Hispanic or Not Latino 
Yes 
 
 
 
 
 
 
* Age calculated at date of informed consent 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 10 of 59 
Listing 4.2: Pre-Busulfan Body Weight 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 2 
Subject 
Number 
Date Performed 
(YYYY-MM-DD) 
Time Performed 
(HH:MM) 
Actual Weight (kg) 
Adjusted ideal body weight 
(AIBW) 
Was Actual Weight OR 
adjusted ideal body weight 
(AIBW) used for the Calculation 
of the Busulfan dose 
 
 
 
 
 
xx-xxxxxx 
YYYY-MM-DD 
HH:MM 
xx.x 
xx.x 
Actual Weight 
xx-xxxxxx 
YYYY-MM-DD 
HH:MM 
xx.x 
xx.x 
Actual Weight 
xx-xxxxxx 
YYYY-MM-DD 
HH:MM 
xx.x 
xx.x 
Actual Weight 
xx-xxxxxx 
YYYY-MM-DD 
HH:MM 
xx.x 
xx.x 
Actual Weight 
xx-xxxxxx 
YYYY-MM-DD 
HH:MM 
xx.x 
xx.x 
Actual Weight 
 
 
 
 
 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 11 of 59 
Listing 5: HIV-1 History 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
Subject Number 
Date of HIV-1 infection 
Diagnosis 
(YYYY-MM-DD) 
Lowest CD4+ 
T Lymphocyte Count 
(cells/μl) 
Date of Lowest CD4+ 
Count 
(YYYY-MM-DD) 
Highest Plasma HIV Viral 
Load 
(copies/mL) 
Date of Highest HIV Viral 
Load 
(YYYY-MM-DD) 
 
 
 
 
 
xx-xxxxxx 
YYYY-MM-DD 
xxx 
YYYY-MM-DD 
xxxxxxx 
YYYY-MM-DD 
xx-xxxxxx 
YYYY-MM-DD 
xxx 
YYYY-MM-DD 
xxxxxxx 
YYYY-MM-DD 
xx-xxxxxx 
YYYY-MM-DD 
xxx 
YYYY-MM-DD 
xxxxxxx 
YYYY-MM-DD 
 
 
 
 
 
NK: Not Known 
 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 12 of 59 
Listing 6: Medical History 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
Subject 
Number 
MH 
No Condition 
Body System Code 
Onset Date 
(YYYY-MM-DD) 
Resolution Date 
(YYYY-MM-DD) 
Ongoing? 
Any Treatment 
Planned? 
xx-xxxxxx 
1 xxxxxxxxxxxxxxxxxxxxxxxxxxx 
Dermatologic 
YYYY-MM-DD 
 
Yes 
No 
3 xxxxxxxxxxxxxxxxxxxxxxxxxxx 
Neurological 
YYYY-MM-DD 
YYYY-MM-DD 
No 
No 
4 xxxxxxxxxxxxxxxxxxxxxxxxxxx 
Other: fainting 
YYYY-MM-DD 
YYYY-MM-DD 
No 
No 
6 xxxxxxxxxxxxxxxxxxxxxxxxxxx 
Allergies/Drug Sensitivity 
NK 
 
Yes 
No 
Etc. 
 
 
 
 
 
 
 
 
 
xx-xxxxxx 
X xxxxxxxxxxxxxxxxxxxxxxxxxxx 
Ears 
NK 
 
Yes 
No 
 
 
 
 
 
NK: Not Known; MH No: Medical History Number 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 13 of 59 
Listing 7: Eligibility 
Protocol: CAL-USA-11 
Population: All Screened 
 
Cohort: Cohort 1 
 
 
 
Inclusion Criteria  
 
 
 
Exclusion Criteria  
 
Subject 
Number 
Evaluation Date 
(YYYY-MM-DD) 
Criteria 
Not Met* Reason Not Met 
 
Criteria 
Met* 
Reason Met 
 
xx-xxxxxx 
YYYY-MM-DD 
xxxxx 
HIV-1 VIRAL RNA LESS THAN 5000 COPIES/ML 
 
 
xx-xxxxxx 
YYYY-MM-DD 
xxxxx 
screening cd4 <500 
xxxxx 
cd4 history <250 
xx-xxxxxx 
YYYY-MM-DD 
xxxxx 
Plasma HIV-1 viral RNA < 5,000 copies/ml reported 
on August 31, 2013 
 
 
xx-xxxxxx 
YYYY-MM-DD 
xxxxx 
CD4 <500 
 
 
xx-xxxxxx 
YYYY-MM-DD 
xxxxx 
HIV-1 RNA > 100,000 copies/ml at Screen 1 reported 
on December 29, 2013 
 
 
xx-xxxxxx 
YYYY-MM-DD 
xxxxx 
viral load 190,000 
 
 
xx-xxxxxx 
YYYY-MM-DD 
xxxxx 
CD4+ T lymphocyte count < 500 at Screen 2 reported 
on September 18, 2013" 
 
 
 
 
 
 
* Inclusion & Exclusion Criteria: refer to Protocol CAL-USA-11, Section 5 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 14 of 59 
Listing 8.1: Pregnancy Test 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
6XEMHFW
1XPEHU
9LVLW
'DWHRI
&ROOHFWLRQ
<<<<00''
7LPHRI
&ROOHFWLRQ
++00
9DULDEOH
6HUXP+&*RU
8ULQH7HVW
5HVXOW
8QLW
&OLQ6LJ
&RPPHQW






xx-xxxxxx
6FUHHQLQJ
YYYY-MM-DD
++00
[[[[[[[[[[[[[[
1HJDWLYH
[[[[[

[[[[[[[[[[[
6FUHHQLQJ
YYYY-MM-DD
++00
[[[[[[[[[[[[[[
1HJDWLYH
[[[[[

[[[[[[[[[[[
*&6)
YYYY-MM-DD
++00
[[[[[[[[[[[[[[
1HJDWLYH
[[[[[

[[[[[[[[[[[






xx-xxxxxx






xx-xxxxxx


















6HUXP+&*WHVWLQJIURPZRPHQRIUHSURGXFWLYHSRWHQWLDOH[FHSWDWFRPPHQFHPHQWRI*&6)EXVXOIDQDQGLQIXVLRQEDVHOLQHZKHQXULQHWHVWLVSHUIRUPHG
&OLQLFDO6LJQLILFDQFH&6 &OLQLFDOO\6LJQLILFDQW1&6 1RW&OLQLFDOO\6LJQLILFDQW
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 15 of 59 
Listing 8.2: Positive Pregnancy Test 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
6XEMHFW
1XPEHU
9LVLW
'DWHRI
&ROOHFWLRQ
<<<<00''
7LPHRI
&ROOHFWLRQ
++00
9DULDEOH
6HUXP+&*RU
8ULQH7HVW
5HVXOW
8QLW
&OLQ6LJ
&RPPHQW






xx-xxxxxx
6FUHHQLQJ
YYYY-MM-DD
++00
[[[[[[[[[[[[[[
3RVLWLYH
[[[[[
1&6
[[[[[[[[[[[
6FUHHQLQJ
YYYY-MM-DD
++00
[[[[[[[[[[[[[[
3RVLWLYH
[[[[[
1&6
[[[[[[[[[[[
*&6)
YYYY-MM-DD
++00
[[[[[[[[[[[[[[
3RVLWLYH
[[[[[
1&6
[[[[[[[[[[[






xx-xxxxxx






xx-xxxxxx


















6HUXP+&*WHVWLQJIURPZRPHQRIUHSURGXFWLYHSRWHQWLDOH[FHSWDWFRPPHQFHPHQWRI*&6)EXVXOIDQDQGLQIXVLRQEDVHOLQHZKHQXULQHWHVWLVSHUIRUPHG
&OLQLFDO6LJQLILFDQFH&6 &OLQLFDOO\6LJQLILFDQW1&6 1RW&OLQLFDOO\6LJQLILFDQW
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 16 of 59 
Listing 9: Chest X-Rays 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
Subject 
Number 
Visit 
Date Performed 
(YYYY-MM-DD) 
Result (If CS, specify)* 
 
 
 
xx-xxxxxx 
Screening 1 
YYYY-MM-DD 
Normal 
Screening 2 
YYYY-MM-DD 
Abnormal – NCS 
 
 
 
xx-xxxxxx 
Screening 1 
YYYY-MM-DD 
Norma; 
Screening 2 
YYYY-MM-DD 
Normal 
 
 
 
*Clinical Significance: CS=Clinically Significant, NCS=Not Clinically Significant 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 17 of 59 
Listing 10: ART Therapy History (regimen overview) 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
Subject Number 
Regimen 
Number 
Drug 
Start Date 
(YYYY-MM-DD) 
Stop Date 
(YYYY-MM-DD) 
Ongoing 
Reason for 
Discontinuation 
of therapy 
Lowest Plasma HIV Viral Load 
Achieved During Regimen 
(copies/mL) 
 
 
 
 
xx-xxxxxx 
1 
3TC 
YYYY-MM-DD 
YYYY-MM-DD 
No 
Toxicity 
<500 
 
D4T 
YYYY-MM-DD 
YYYY-MM-DD 
No 
 
INVIRASE 
YYYY-MM-DD 
YYYY-MM-DD 
No 
2 
CRIXIVAN 
YYYY-MM-DD 
YYYY-MM-DD 
No 
Toxicity 
<500 
 
COMBIVIR 
YYYY-MM-DD 
YYYY-MM-DD 
No 
3 
COMBIVIR 
YYYY-MM-DD 
YYYY-MM-DD 
No 
Treatment fatigue 
<50 
 
SUSTIVA 
YYYY-MM-DD 
YYYY-MM-DD 
No 
xx-xxxxxx 
1 
Complera 
YYYY-MM-DD 
YYYY-MM-DD 
No 
Treatment fatigue 
<20 
xx-xxxxxx 
1 
ATRIPLA 
YYYY-MM-DD 
YYYY-MM-DD 
No 
Toxicity 
<20 
2 
COMPLERA 
YYYY-MM-DD 
YYYY-MM-DD 
No 
Treatment fatigue 
<20 
xx-xxxxxx 
1 
truvada 
YYYY-MM-DD 
YYYY-MM-DD 
No 
Treatment fatigue 
<20 
 
isentress 
YYYY-MM-DD 
YYYY-MM-DD 
No 
xx-xxxxxx 
1 
Miraviroc 
YYYY-MM-DD 
YYYY-MM-DD 
No 
Toxicity 
<50 
2 
Atripla 
YYYY-MM-DD 
YYYY-MM-DD 
No 
Toxicity 
<75 
3 
complera 
YYYY-MM-DD 
YYYY-MM-DD 
No 
Treatment fatigue 
<75 
xx-xxxxxx 
1 
stribild 
YYYY-MM-DD 
YYYY-MM-DD 
No 
Treatment fatigue 
<20 
2 
stribild 
YYYY-MM-DD 
YYYY-MM-DD 
No 
Treatment fatigue 
44 
xx-xxxxxx 
1 
ISENTRESS 
YYYY-MM-DD 
YYYY-MM-DD 
No 
Treatment fatigue 
<20 
 
TRUVADA 
YYYY-MM-DD 
YYYY-MM-DD 
No 
xx-xxxxxx 
1 
truvada 
YYYY-MM-DD 
YYYY-MM-DD 
No 
Toxicity 
<40 
 
miraviroc 
YYYY-MM-DD 
YYYY-MM-DD 
No 
2 
darunavir 
YYYY-MM-DD 
YYYY-MM-DD 
No 
Toxicity 
unk 
 
ritonavir 
YYYY-MM-DD 
YYYY-MM-DD 
No 
3 
truvada 
YYYY-MM-DD 
YYYY-MM-DD 
No 
Treatment fatigue 
<40 
 
raltegravir 
YYYY-MM-DD 
YYYY-MM-DD 
No 
 
 
 
 
NK: Not Known 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 18 of 59 
Listing 11: Transduced CD4+ Cell Product Dose (Transduction efficiency, viability, cell numbers for Ttn) 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
Subject 
Number 
Date of TCP 
Infusion 
(YYYY-MM-DD) 
Total Number of Cells Infused1 
Viability 
(%)2 
Purity of cells 
infused 
Transduction Efficiency of 
Cells Infused (%) 
Cal-1 Vector Copy Number 
(VCN) per Ttn cell (VCN/cell) 
Absolute 
(x108 cells) 
Expressed as 
cells/kg body weight 
(x106 cells/kg) 
 
 
 
 
 
 
 
xx-xxxxxx 
YYYY-MM-DD 
xx 
xx.x 
xx 
xx.x 
xx.x 
xx.x 
xx-xxxxxx 
YYYY-MM-DD 
xx 
xx.x 
xx 
xx.x 
xx.x 
xx.x 
xx-xxxxxx 
YYYY-MM-DD 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx-xxxxxx 
YYYY-MM-DD 
xx.x 
xx.x 
xx 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
 
 
1 Viable, transduced cells (viability based on pre-thaw viability) 
2 Pre-thaw viability of Ttn cells (%) 
TCP: Transduced Cell Product 
Ttn: Cal-1 transduced CD4+ T lymphocytes 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 19 of 59 
Listing 12: Transduced CD34+ Cell Product Dose (Transduction efficiency, viability, cell numbers for HSPCtn) 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
Subject 
Number 
Date of TCP 
Infusion 
(YYYY-MM-DD) 
Total Number of Cells Infused1 
Viability 
(%)2 
Purity of cells 
infused 
Transduction Efficiency 
of Cells Infused (%) 
Cal-1 Vector Copy 
Number (VCN) per Ttn 
cell (VCN/cell) 
Was the CD34+ 
back-up apheresis 
product infused 
Absolute 
(x108 cells) 
Expressed as 
cells/kg body 
weight 
(x106 cells/kg) 
 
 
 
 
 
 
 
xx-xxxxxx 
YYYY-MM-DD 
xx 
xx.x 
xx 
xx.x 
xx.x 
xx.x 
- 
xx-xxxxxx 
YYYY-MM-DD 
xx 
xx.x 
xx 
xx.x 
xx.x 
xx.x 
- 
xx-xxxxxx 
YYYY-MM-DD 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
- 
xx-xxxxxx 
YYYY-MM-DD 
xx.x 
xx.x 
xx 
xx.x 
xx.x 
xx.x 
- 
 
 
 
 
 
 
- 
 
1 Viable, transduced cells (viability based on pre-thaw viability) 
2 Pre-thaw viability of HSPCtn cells (%) 
TCP: Transduced Cell Product 
HSPCtn: Cal-1 transduced CD34+ Hematopoietic stem/progenitor cells 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 20 of 59 
Listing 13.1: G-CSF Therapy 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
Subject 
Number 
Visit 
Was G-CSF 
Administered? 
Dose 
Administered 
(μg/kg) 
Total Daily 
Dose 
Administered 
(μg) 
Full Dose 
Administered? 
Date/ Time Administered 
(YYYY-MM-DD) / HH:MM 
Time Second Dose 
Administered 
HH:MM 
Was the White blood 
cell count on Day 4 
of G-CSF < 
75,000x10e9/mL? 
 
 
 
 
 
 
 
xx-xxxxxx 
G-CSF 1 
Yes 
10μg/kg QD 
xxx 
- 
YYYY-MM-DD/ HH:MM 
HH:MM 
 
G-CSF 2 
Yes 
10μg/kg QD 
- 
Yes 
YYYY-MM-DD/ HH:MM 
HH:MM 
 
G-CSF 3 
Yes 
10μg/kg QD 
- 
Yes 
YYYY-MM-DD/ HH:MM 
HH:MM 
 
G-CSF 4 
Yes 
10μg/kg QD 
- 
Yes 
YYYY-MM-DD/ HH:MM 
HH:MM 
 
CD34+ Apheresis 
 
 
 
 
 
 
xx 
 
 
 
 
 
 
 
xx-xxxxxx 
G-CSF 1 
Yes 
10μg/kg QD 
xxx 
- 
YYYY-MM-DD/ HH:MM 
HH:MM 
 
G-CSF 2 
Yes 
10μg/kg QD 
- 
Yes 
YYYY-MM-DD/ HH:MM 
HH:MM 
 
G-CSF 3 
Yes 
10μg/kg QD 
- 
Yes 
YYYY-MM-DD/ HH:MM 
HH:MM 
 
G-CSF 4 
Yes 
10μg/kg QD 
- 
Yes 
YYYY-MM-DD/ HH:MM 
HH:MM 
 
CD34+ Apheresis 
 
 
 
 
 
 
xx 
 
 
 
 
 
 
 
xx-xxxxxx 
G-CSF 1 
Yes 
10μg/kg QD 
xxx 
- 
YYYY-MM-DD/ HH:MM 
HH:MM 
 
G-CSF 2 
Yes 
10μg/kg QD 
- 
Yes 
YYYY-MM-DD/ HH:MM 
HH:MM 
 
G-CSF 3 
Yes 
10μg/kg QD 
- 
Yes 
YYYY-MM-DD/ HH:MM 
HH:MM 
 
G-CSF 4 
Yes 
10μg/kg QD 
- 
Yes 
YYYY-MM-DD/ HH:MM 
HH:MM 
 
CD34+ Apheresis 
 
 
 
 
 
 
xx 
 
 
 
 
 
 
 
xx-xxxxxx 
G-CSF 1 
Yes 
10μg/kg QD 
xxxxx 
- 
YYYY-MM-DD/ HH:MM 
HH:MM 
 
G-CSF 2 
Yes 
10μg/kg QD 
- 
Yes 
YYYY-MM-DD/ HH:MM 
HH:MM 
 
G-CSF 3 
Yes 
5μg/kg BD 
- 
No 
YYYY-MM-DD/ HH:MM 
HH:MM 
 
G-CSF 4 
Yes 
5μg/kg BD 
- 
Yes 
YYYY-MM-DD/ HH:MM 
HH:MM 
 
CD34+ Apheresis 
 
 
 
 
 
 
xx 
 
 
 
 
 
 
 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 21 of 59 
Listing 13.2: Plerixafor Therapy 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 3 
 
Subject 
Number 
Visit 
Total Daily Dose 
Administered 
(μg) 
Date/ Time Administered 
(YYYY-MM-DD) / HH:MM 
 
 
xx-xxxxxx 
G-CSF 4 & plerixafor 
xxx 
YYYY-MM-DD/ HH:MM 
xx-xxxxxx 
G-CSF 4 & plerixafor 
xxx 
YYYY-MM-DD/ HH:MM 
xx-xxxxxx 
G-CSF 4 & plerixafor 
xxx 
YYYY-MM-DD/ HH:MM 
xx-xxxxxx 
G-CSF 4 & plerixafor 
xxx 
YYYY-MM-DD/ HH:MM 
xx-xxxxxx 
G-CSF 4 & plerixafor 
xxx 
YYYY-MM-DD/ HH:MM 
xx-xxxxxx 
G-CSF 4 & plerixafor 
xxx 
YYYY-MM-DD/ HH:MM 
xx-xxxxxx 
G-CSF 4 & plerixafor 
xxx 
YYYY-MM-DD/ HH:MM 
xx-xxxxxx 
G-CSF 4 & plerixafor 
xxx 
YYYY-MM-DD/ HH:MM 
xx-xxxxxx 
G-CSF 4 & plerixafor 
xxx 
YYYY-MM-DD/ HH:MM 
 
 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 22 of 59 
Listing 14.1: Apheresis - CD4+ 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
Subject 
Number 
Visit 
Apheresis 
Completed 
Successfully? 
(if no, 
specify) 
Date Performed 
(YYYY-MM-DD) Star/Stop Time 
Venous 
Access 
Location 
Filtration Volume (L) 
Number of CD4+ 
Lymphocytes 
Collected 
(x108 cells) 
CD4+ % T-
lymphocytes (%) 
Total number of 
target CD4+ T-
lymphocytes 
collected (x10e8) 
(x10e8) 
 
 
 
 
 
 
 
xx-xxxxxx CD34+ Apheresis Yes 
YYYY-MM-DD HH:MM/ HH:MM 
Central 
venous 
x.x 
x.x 
xx 
xx 
 
 
 
 
 
 
 
xx-xxxxxx CD34+ Apheresis Yes 
YYYY-MM-DD HH:MM/ HH:MM 
Central 
venous 
x.xxx 
xx.x 
xx 
xx 
 
 
 
 
 
 
 
xx-xxxxxx CD34+ Apheresis Yes 
YYYY-MM-DD HH:MM/ HH:MM 
Central 
venous 
x 
xx 
xx 
xx 
 
 
 
 
 
 
 
xx-xxxxxx CD34+ Apheresis Yes 
YYYY-MM-DD HH:MM/ HH:MM 
Central 
venous 
x 
xx.x 
xx 
xx 
 
 
 
 
 
 
 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
Programming Note: Repeat this listing for: 
14.2 
Apheresis - CD34+ 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 23 of 59 
Listing 14.2: Apheresis - CD34+ 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 24 of 59 
Listing 15.1: Busulfan Dosing 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 2 
 
Subject 
Number 
Busulfan Dose 
Date Administered 
(YYYY-MM-DD) 
Total Volume of the 
Intended Busulfan Dose 
(ml) 
Residual Volume of the 
IV Line (ml) 
Infusion Pump Flow 
Rate (ml/hour) 
Dose Interrupted 
 
 
 
 
 
 
xx-xxxxxx 
1 x 4mg/kg 
YYYY-MM-DD 
xx 
xx 
xx 
No 
xx-xxxxxx 
1 x 4mg/kg 
YYYY-MM-DD 
xx 
xx 
xx 
No 
xx-xxxxxx 
1 x 4mg/kg 
YYYY-MM-DD 
xx 
xx 
xx 
No 
xx-xxxxxx 
1 x 4mg/kg 
YYYY-MM-DD 
xx 
xx 
xx 
No 
xx-xxxxxx 
1 x 4mg/kg 
YYYY-MM-DD 
xx 
xx 
xx 
No 
xx-xxxxxx 
1 x 4mg/kg 
YYYY-MM-DD 
xx 
xx 
xx 
No 
xx-xxxxxx 
1 x 4mg/kg 
YYYY-MM-DD 
xx 
xx 
xx 
Yes 
xx-xxxxxx 
1 x 4mg/kg 
YYYY-MM-DD 
xx 
xx 
xx 
Yes 
xx-xxxxxx 
1 x 4mg/kg 
YYYY-MM-DD 
xx 
xx 
xx 
Yes 
xx-xxxxxx 
1 x 4mg/kg 
YYYY-MM-DD 
xx 
xx 
xx 
Yes 
 
 
 
 
 
 
Note: Cohort 1 not included as this cohort did not receive Busulfan 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 25 of 59 
 
Listing 15.1: Busulfan Interruptions 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 2 
 
Subject 
Number 
Busulfan Dose 
Date Administered 
(YYYY-MM-DD) 
Infusion Interruption 
Time (HH:MM) 
Infusion restart time 
(HH:MM) 
Reason for Interruption 
 
 
 
 
 
xx-xxxxxx 
1 x 4mg/kg 
YYYY-MM-DD 
HH:MM 
HH:MM 
xxxxxxxxxxxxxxxxxxxxxxxx 
xx-xxxxxx 
1 x 4mg/kg 
YYYY-MM-DD 
HH:MM 
HH:MM 
xxxxxxxxxxxxxxxxxxxxxxxx 
xx-xxxxxx 
1 x 4mg/kg 
YYYY-MM-DD 
HH:MM 
HH:MM 
xxxxxxxxxxxxxxxxxxxxxxxx 
xx-xxxxxx 
1 x 4mg/kg 
YYYY-MM-DD 
HH:MM 
HH:MM 
xxxxxxxxxxxxxxxxxxxxxxxx 
xx-xxxxxx 
1 x 4mg/kg 
YYYY-MM-DD 
HH:MM 
HH:MM 
xxxxxxxxxxxxxxxxxxxxxxxx 
xx-xxxxxx 
1 x 4mg/kg 
YYYY-MM-DD 
HH:MM 
HH:MM 
xxxxxxxxxxxxxxxxxxxxxxxx 
xx-xxxxxx 
1 x 4mg/kg 
YYYY-MM-DD 
HH:MM 
HH:MM 
xxxxxxxxxxxxxxxxxxxxxxxx 
xx-xxxxxx 
1 x 4mg/kg 
YYYY-MM-DD 
HH:MM 
HH:MM 
xxxxxxxxxxxxxxxxxxxxxxxx 
xx-xxxxxx 
1 x 4mg/kg 
YYYY-MM-DD 
HH:MM 
HH:MM 
xxxxxxxxxxxxxxxxxxxxxxxx 
xx-xxxxxx 
1 x 4mg/kg 
YYYY-MM-DD 
HH:MM 
HH:MM 
xxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
Note: Cohort 1 not included as this cohort did not receive Busulfan 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 26 of 59 
Listing 15.3: Busulfan Administration and Pharmacokinetics 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 2 
 
Subject 
Number 
Date 
Administered 
(YYYY-MM-DD) 
Infusion Start 
Time 
(HH:MM) 
Infusion End 
Time 
(HH:MM) 
Total Dose 
Administered 
(mg) 
Scheduled PK 
Testing Time 
Actual Collection 
Time 
(HH:MM) 
PK AUC 
(umol/min) 
Clearance Rate 
(mL/min/Kg) 
Concentration at 
Steady State 
(ng/mL) 
xx-xxxxxx 
YYYY-MM-DD 
HH:MM 
HH:MM 
xxx.x 
Pre-Dose 
- 
xxxxx 
x.xx 
xxxxx 
 
 
 
 
EOI 
HH:MM 
 
 
 
 
 
 
 
EOI + 15 minutes 
HH:MM 
 
 
 
 
 
 
 
EOI + 1 hour 
HH:MM 
 
 
 
 
 
 
 
EOI + 2 hour 
HH:MM 
 
 
 
 
 
 
 
EOI + 3 hour 
HH:MM 
 
 
 
 
 
 
 
EOI + 4 hour 
HH:MM 
 
 
 
 
 
 
 
EOI + 5 hour 
HH:MM 
 
 
 
 
 
 
 
 
 
 
 
xx-xxxxxx 
YYYY-MM-DD 
HH:MM 
HH:MM 
xxx 
Pre-Dose 
- 
xxxxx 
x.xx 
xxxxx 
 
 
 
 
EOI 
HH:MM 
 
 
 
 
 
 
 
EOI + 15 minutes 
HH:MM 
 
 
 
 
 
 
 
EOI + 1 hour 
HH:MM 
 
 
 
 
 
 
 
EOI + 2 hour 
HH:MM 
 
 
 
 
 
 
 
EOI + 3 hour 
HH:MM 
 
 
 
 
 
 
 
EOI + 4 hour 
HH:MM 
 
 
 
 
 
 
 
EOI + 5 hour 
HH:MM 
 
 
 
 
 
 
 
 
 
 
 
xx-xxxxxx 
YYYY-MM-DD 
HH:MM 
HH:MM 
xxx.xx 
Pre-Dose 
- 
xxxxx 
x.xx 
xxxxx 
 
 
 
 
EOI 
HH:MM 
 
 
 
 
 
 
 
EOI + 15 minutes 
HH:MM 
 
 
 
 
 
 
 
EOI + 1 hour 
HH:MM 
 
 
 
 
 
 
 
EOI + 2 hour 
HH:MM 
 
 
 
 
 
 
 
EOI + 3 hour 
HH:MM 
 
 
 
 
 
 
 
EOI + 4 hour 
HH:MM 
 
 
 
 
 
 
 
EOI + 5 hour 
HH:MM 
 
 
 
 
 
 
 
 
 
 
 
Note: Cohort 1 not included as this cohort did not receive Busulfan 
EOI: End of Infusion; AUC: Area Under the Curve 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 27 of 59 
Listing 16: Cal-1 Marking/Expression - Peripheral Blood 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
 
Cal-1 Marking   
(WPRE qPCR) 
 
Cal-1 C46 Expression   
(C46 RT-qPCR) 
 
Cal-1 sh5 Expression   
(sh5 RT-qPCR) 
Subject Number 
Visit 
Collection Date 
(YYYY-MM-DD) 
Result 
Quantification 
(Copies/cell) 
Quantification 
(%) 
Result 
Quantification 
(Relative Expression) 
Result 
Quantification 
(Relative Expression) 
 
 
 
 
 
 
 
 
xx-xxxxxx 
Infusion (Day 0) 
YYYY-MM-DD 
Not detected 
 
 
Not detected 
 
Not detected 
 
Week 4 
YYYY-MM-DD 
Detected, NQ 
 
 
Not detected 
 
Not detected 
 
Week 12 
YYYY-MM-DD 
Detected, NQ 
 
 
Not detected 
 
Not detected 
 
Week 24 
YYYY-MM-DD 
Not detected 
 
 
Not detected 
 
Not detected 
 
Week 32 
YYYY-MM-DD 
Detected, NQ 
 
 
Not detected 
 
Not detected 
 
Week 40 
YYYY-MM-DD 
Detected, NQ 
 
 
Not detected 
 
Not detected 
 
Week 48 
YYYY-MM-DD 
Not detected 
 
 
Not detected 
 
Detected, NQ 
 
 
 
 
 
 
 
 
 
xx-xxxxxx 
Infusion (Day 0) 
YYYY-MM-DD 
Not detected 
 
 
Not detected 
 
Not detected 
 
Week 4 
YYYY-MM-DD 
Detected, NQ 
 
 
Not detected 
 
Not detected 
 
Week 12 
YYYY-MM-DD 
Detected 
x.xxxxx 
x.xx 
Not detected 
 
Not detected 
 
Week 24 
YYYY-MM-DD 
Not detected 
 
 
Not detected 
 
Detected, NQ 
 
Week 32 
YYYY-MM-DD 
Not detected 
 
 
Not detected 
 
Not detected 
 
Week 40 
YYYY-MM-DD 
Detected, NQ 
 
 
Not detected 
 
Not detected 
 
Week 48 
YYYY-MM-DD 
Not detected 
 
 
Not detected 
 
Not detected 
 
Week 40 
YYYY-MM-DD 
Detected, NQ 
 
 
Not detected 
 
Not detected 
 
 
 
 
 
 
 
 
 
NQ: Not Quantifiable 
Mandatory Fields: Cal-1 Marking 
Optional Fields: Cal-1 Expression 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 28 of 59 
Listing 17: Cal-1 Marking/Expression – Bone Marrow 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
 
Cal-1 Marking  
(WPRE QPCR) 
Cal-1 C46 Expression  
(C46 RT-qPCR) 
Cal-1 sh5 Expression  
(sh5 RT-qPCR) 
Subject Number 
Visit 
Date BMA Obtained 
(YYYY-MM-DD) 
Result 
Quantification 
(Copies/cell) 
Result 
Quantification 
(Relative Expression) 
Result 
Quantification 
(Relative Expression) 
 
 
 
 
 
 
 
xx-xxxxxx 
Week 12 
YYYY-MM-DD 
Not detected 
 
Not detected 
 
Not detected 
 
xx-xxxxxx 
Week 12 
YYYY-MM-DD 
Not detected 
 
Not detected 
 
Detected, NQ 
 
xx-xxxxxx 
Week 12 
YYYY-MM-DD 
Not detected 
 
Not detected 
 
Detected, NQ 
 
xx-xxxxxx 
Week 12 
YYYY-MM-DD 
Detected 
0.xxxxxxx 
Not detected 
 
Detected, NQ 
 
 
 
 
 
 
 
 
NQ: Not Quantifiable 
BMA: Bone Marrow Aspirate 
Mandatory Fields: Cal-1 Marking 
Optional Fields: Cal-1 Expression 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 29 of 59 
Listing 18: Cal-1 Marking/Expression – GALT 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
 
 
Cal-1 Marking  
(WPRE QPCR) 
Cal-1 C46 Expression  
(C46 RT-qPCR) 
Cal-1 sh5 Expression  
(sh5 RT-qPCR) 
Subject Number 
Visit 
Date GALT 
Biopsy Obtained 
(YYYY-MM-DD) 
Location 
Result 
Quantification 
(Copies/cell) 
Result 
Quantification 
(Relative Expression) 
Result 
Quantification 
(Relative Expression) 
 
 
 
 
 
 
 
xx-xxxxxx 
Week 12 
YYYY-MM-DD 
1: 10-15cm 
Detected 
x.xxxxx 
Not detected 
 
Detected, NQ 
 
 
2: 25-35cm 
Detected 
x.xxxxx 
Not detected 
 
Detected, NQ 
 
 
 
 
 
 
 
 
xx-xxxxxx 
Week 12 
YYYY-MM-DD 
1: 10-15cm 
Detected 
x.xxxxx 
Not detected 
 
Not detected 
 
 
2: 25-35cm 
Detected 
x.xxxxx 
Not detected 
 
Not detected 
 
 
 
 
 
 
 
 
xx-xxxxxx 
Week 12 
YYYY-MM-DD 
1: 10-15cm 
Detected 
x.xxxxx 
Not detected 
 
Not detected 
 
 
2: 25-35cm 
Detected 
x.xxxxx 
Not detected 
 
Not detected 
 
 
 
 
 
 
 
 
xx-xxxxxx 
Week 12 
YYYY-MM-DD 
1: 10-15cm 
Not detected 
 
Not detected 
 
Detected, NQ 
 
 
2: 25-35cm 
Not detected 
 
Not detected 
 
Detected, NQ 
 
 
 
 
 
 
 
 
NQ: Not Quantifiable 
Mandatory Fields: Cal-1 Marking; Optional Fields: Cal-1 Expression 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 30 of 59 
Listing 19.1: Cal-1 Marking/Expression – Subsets Monocytes 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
 
Cal-1 Marking  
(WPRE QPCR) 
 
Cal-1 C46 Expression  
(C46 RT-qPCR) 
 
Cal-1 sh5 Expression  
(sh5 RT-qPCR) 
Subject 
Number 
Visit 
Collection Date 
(YYYY-MM-DD) 
Population 
Purity 
(CD14+/CD45+) 
(%) 
Result 
Quantification 
(Copies/cell) 
Result 
Quantification 
(Relative Expression)  
Result 
Quantification 
(Relative Expression) 
 
 
 
 
 
 
 
 
 
xx-xxxxxx Infusion (Day 0) 
YYYY-MM-DD 
xx.x 
Detected, NQ 
 
Not detected 
 
 Detected, NQ 
 
Week 4 
YYYY-MM-DD 
xx.x 
Not detected 
 
Not detected 
 
 
Detected 
x.xxxxx 
Week 12 
YYYY-MM-DD 
xx.x 
Detected, NQ 
 
Not detected 
 
 Detected, NQ 
 
Week 24 
YYYY-MM-DD 
xx.x 
Not detected 
 
Not detected 
 
 Not detected 
 
Week 48 
YYYY-MM-DD 
xx.x 
Not detected 
 
Not detected 
 
 Detected, NQ 
 
 
 
 
 
 
 
 
 
 
xx-xxxxxx Infusion (Day 0) 
YYYY-MM-DD 
xx.x 
Detected, NQ 
 
Not detected 
 
 Detected, NQ 
 
Week 4 
YYYY-MM-DD 
xx.x 
Detected, NQ 
 
Not detected 
 
 Not detected 
 
Week 12 
YYYY-MM-DD 
xx.x 
Not detected 
 
Not detected 
 
 Not detected 
 
Week 24 
YYYY-MM-DD 
xx.x 
Not detected 
 
Not detected 
 
 Not detected 
 
Week 48 
YYYY-MM-DD 
xx.x 
Detected 
x.xxxxx 
Not detected 
 
 Not detected 
 
Early 
discontinuation / 
withdrawal 
YYYY-MM-DD 
xx.x 
Detected, NQ 
 
Not detected 
 
 
Detected 
x.xxxxx 
 
 
 
 
 
 
 
 
 
NQ: Not Quantifiable 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
Programming Note: Repeat this listing for: 
19.2 
Cal-1 Marking/Expression – Subsets: Granulocytes 
19.3 
Cal-1 Marking/Expression – Subsets: CD4+ Lymphocytes 
19.4 
Cal-1 Marking/Expression – Subsets: CD8+ Lymphocytes 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 31 of 59 
Listing 19.2: Cal-1 Marking/Expression – Subsets: Granulocytes 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 32 of 59 
Listing 19.3: Cal-1 Marking/Expression – Subsets: CD4+ Lymphocytes 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 33 of 59 
Listing 19.4: Cal-1 Marking/Expression – Subsets: CD8+ Lymphocytes 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 34 of 59 
Listing 20.1: Serious Adverse Events, including event narratives 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
Subject 
Number 
AE 
No. 
SOC/ Preferred Term/ 
Verbatim Term 
Start Date 
(YYYY-MM-DD) 
Stop Date 
(YYYY-MM-DD) 
CTC 
Grade 
Action Taken 
Outcome 
Causality 
(Related to 
Cal-1) 
Causality 
(Related to 
Procedure / 
Required 
Medication) 
Details 
 
 
 
 
 
 
 
 
 
xx-xxxxxx 1 
ZZZZZZZZZZZZ/ 
YYYYYYYYYYY/ 
ZZZZZZZZZZZZ 
YYYY-MM-DD 
YYYY-MM-DD 
Mild 
None 
Resolved 
Not related Very likely: 
GCSF 
xxxxxxxxxxxxxxx 
2 
ZZZZZZZZZZZZ/ 
YYYYYYYYYYY/ 
ZZZZZZZZZZZZ 
YYYY-MM-DD 
YYYY-MM-DD 
Mild 
None 
Resolved 
Very likely 
Not related 
xxxxxxxxxxxxxxx 
3 
ZZZZZZZZZZZZ/ 
YYYYYYYYYYY/ 
ZZZZZZZZZZZZ 
YYYY-MM-DD 
- 
Mild 
Concomitant 
medication 
Ongoing 
Possible 
Not related 
xxxxxxxxxxxxxxx 
4 
ZZZZZZZZZZZZ/ 
YYYYYYYYYYY/ 
ZZZZZZZZZZZZ 
YYYY-MM-DD 
- 
Mild 
None 
Ongoing 
Not related Not related 
xxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
SOC: System Organ Class, AE No.: Adverse Event Number; CTC: Common Terminology Criteria; NK: Not Known 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 35 of 59 
Listing 20.2: Deaths 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
Subject 
Number 
AE 
No. 
SOC/ Preferred Term/ Verbatim 
Term 
Start Date 
(YYYY-MM-DD) 
Stop Date 
(YYYY-MM-DD) 
Death Date 
(YYYY-MM-DD) 
Autopsy Performed 
Autopsy Date 
(YYYY-MM-DD) 
Type of Tissue 
Collected 
 
 
 
 
 
 
 
 
xx-xxxxxx 
1 
ZZZZZZZZZZZZ/ YYYYYYYYYYY/ 
ZZZZZZZZZZZZ 
YYYY-MM-DD 
YYYY-MM-DD 
YYYY-MM-DD 
Yes 
YYYY-MM-DD 
xxxxxxxx 
2 
ZZZZZZZZZZZZ/ YYYYYYYYYYY/ 
ZZZZZZZZZZZZ 
YYYY-MM-DD 
YYYY-MM-DD 
YYYY-MM-DD 
No 
YYYY-MM-DD 
xxxxxxxx 
 
 
 
 
 
 
 
 
SOC: System Organ Class, AE No.: Adverse Event Number; CTC: Common Terminology Criteria; NK: Not Known 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 36 of 59 
Listing 21.1: Adverse Events (All Grades) 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
Subject 
Number 
AE 
No. 
SOC/ Preferred Term/ 
Verbatim Term 
Start Date 
(YYYY-MM-DD) 
Stop Date 
(YYYY-MM-DD) 
Serious 
CTC 
Grade 
Action Taken 
Outcome 
Causality 
(Related to 
Cal-1) 
Causality 
(Related to 
Procedure / 
Required 
Medication) 
Details 
 
 
 
 
 
 
 
 
 
 
xx-xxxxxx 1 
ZZZZZZZZZZZZ/ 
YYYYYYYYYYY/ 
ZZZZZZZZZZZZ 
YYYY-MM-DD YYYY-MM-DD 
No 
Mild 
None 
Resolved Not related Very likely: 
GCSF 
xxxxxxxxxxxxxxx 
2 
ZZZZZZZZZZZZ/ 
YYYYYYYYYYY/ 
ZZZZZZZZZZZZ 
YYYY-MM-DD YYYY-MM-DD 
NO 
Mild 
None 
Resolved 
Very likely Not related 
xxxxxxxxxxxxxxx 
3 
ZZZZZZZZZZZZ/ 
YYYYYYYYYYY/ 
ZZZZZZZZZZZZ 
YYYY-MM-DD 
- 
Yes 
Mild 
Concomitant 
medication 
Ongoing 
Possible 
Not related 
xxxxxxxxxxxxxxx 
4 
ZZZZZZZZZZZZ/ 
YYYYYYYYYYY/ 
ZZZZZZZZZZZZ 
YYYY-MM-DD 
- 
No 
Mild 
None 
Ongoing 
Not related Not related 
xxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
SOC: System Organ Class, AE No.: Adverse Event Number; CTC: Common Terminology Criteria; NK: Not Known 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
Programming Note: Repeat this listing for: 
21.2 
Adverse Events (Grades 3 and /or 4) 
21.3 
Related Adverse Events (Grades 3 and /or 4) 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 37 of 59 
Listing 21.2: Adverse Events (Grades 3 and /or 4) 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 38 of 59 
Listing 21.3: Related Adverse Events (Grades 3 and /or 4) 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 39 of 59 
 
Listing 22.1: Concomitant Medication 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
Subject 
Number 
Taken 
any 
con 
med? 
Con 
med 
No. 
Preferred Term/ 
Medication Name 
Dose 
Unit 
Frequency 
Route 
Start Date 
(YYYY-MM-
DD) 
Stop Date 
(YYYY-MM-
DD) 
Indication 
Continuing? 
Stopped 
Prior to 
Apheresis? 
 
 
 
 
 
 
 
 
 
 
xx-xxxxxx 
Yes 
16 
ZZZZZZZZZZZZ/ 
YYYYYYYYYYY 
xxx 
MG 
PRN 
Oral 
YYYY-MM-DD 
- 
AE 
Yes 
No 
 
19 
ZZZZZZZZZZZZ/ 
YYYYYYYYYYY 
x 
tab 
Twice a day 
Oral 
YYYY-MM-DD YYYY-MM-DD AE 
No 
No 
 
20 
ZZZZZZZZZZZZ/ 
YYYYYYYYYYY 
x 
tab 
Twice a day 
Oral 
YYYY-MM-DD YYYY-MM-DD AE 
No 
No 
 
22 
ZZZZZZZZZZZZ/ 
YYYYYYYYYYY 
xx 
mg 
PRN 
Oral 
YYYY-MM-DD 
- 
AE 
Yes 
Yes 
 
24 
ZZZZZZZZZZZZ/ 
YYYYYYYYYYY 
x 
TAB 
Once daily 
Oral 
YYYY-MM-DD 
- 
AE 
Yes 
No 
 
4 
ZZZZZZZZZZZZ/ 
YYYYYYYYYYY 
x 
tab 
Once daily 
Oral 
YYYY-MM-DD 
- 
Gen. Wellbeing 
Yes 
No 
 
5 
ZZZZZZZZZZZZ/ 
YYYYYYYYYYY 
x 
tab 
Once daily 
Oral 
YYYY-MM-DD 
- 
Gen. Wellbeing 
Yes 
No 
 
 
 
 
 
 
 
 
 
 
Con med No. = Concomitant Medication number 
Con med = Concomitant Medication; NK = Not Known 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 40 of 59 
Listing 22.2: Concomitant Procedures and Therapies 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
Subject 
Number 
Procedure 
No. 
Procedure Date 
(YYYY-MM-DD) 
Procedure 
Indication 
Adverse Event 
Medical History 
 
 
 
 
xx-xxxxxx 
1 
YYYY-MM-DD 
xxxxxxxxxxxxxxxxxx 
AE 
xxxxxxxxxxxxxxxx 
 
2 
YYYY-MM-DD 
xxxxxxxxxxxxxxxxxx 
Other – xxxxx 
 
 
3 
YYYY-MM-DD 
xxxxxxxxxxxxxxxxxx 
AE 
xxxxxxxxxxxxxxxx 
 
4 
YYYY-MM-DD 
xxxxxxxxxxxxxxxxxx 
AE 
xxxxxxxxxxxxxxxx 
 
5 
YYYY-MM-DD 
xxxxxxxxxxxxxxxxxx 
AE 
xxxxxxxxxxxxxxxx 
 
6 
YYYY-MM-DD 
xxxxxxxxxxxxxxxxxx 
AE 
xxxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 41 of 59 
Listing 23.1: Laboratory – Hematology 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
Subject 
Number Visit 
Date of 
Collection 
(YYYY-MM-DD) 
Time of 
Collection 
(HH:MM) Variable 
Result 
Unit 
LLN 
ULN 
Flag* 
Clin. 
Sig.** Comment 
 
 
 
 
 
 
 
 
 
xx-xxxxxx Screening 1 
YYYY-MM-DD 
HH:MM 
Hemoglobin 
xx.x 
g/dL 
12.5 
17.0 
- 
- 
 
 
 
Hematocrit 
xx.x 
% 
36.0 
50.0 
- 
- 
 
 
 
Platelet Count 
xx.x 
10^3/uL 
140 
415 
- 
- 
 
 
 
Red Blood Cells 
xx.x 
10^6/uL 
4.10 
5.60 
- 
- 
 
 
 
White Blood Cells 
xx.x 
10^3/uL 
4.00 
10.50 
- 
- 
 
 
 
Neutrophils Absolute 
xx.x 
10^3/uL 
1.80 
7.80 
- 
- 
 
 
 
Neutrophils Percent 
xx.x 
% 
40 
74 
- 
- 
 
 
 
Lymphocytes Absolute 
xx.x 
10^3/uL 
0.70 
4.50 
- 
- 
 
 
 
Lymphocytes Percent 
xx.x 
% 
14 
46 
- 
- 
 
 
 
Monocytes Absolute 
xx.x 
10^3/uL 
0.10 
1.00 
- 
- 
 
 
 
Monocytes Percent 
xx.x 
% 
4 
13 
- 
- 
 
 
 
Eosinophils Absolute 
xx.x 
10^3/uL 
0.00 
0.40 
- 
- 
 
 
 
Eosinophils Percent 
xx.x 
% 
0 
7 
- 
- 
 
 
 
Basophils Absolute 
xx.x 
10^3/uL 
0.00 
0.20 
- 
- 
 
 
 
Basophils Percent 
xx.x 
% 
0 
3 
- 
- 
 
 
 
 
 
 
 
 
 
 
LLN=Lower Limit of Normal; ULN=Upper Limit of Normal 
* Flag: H=High, L=Low 
** Clinical Significance: CS=Clinically Significant, NCS: Not Clinically Significant 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
Programming Note: Repeat this listing for: 
23.2 
Laboratory – Hematology (Abnormal only) 
24.1 
Laboratory – Biochemistry 
24.2 
Laboratory – Biochemistry (Abnormal only) 
25 
Laboratory – Lymphocyte phenotype 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 42 of 59 
Listing 23.2: Laboratory – Hematology (Abnormal only) 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 43 of 59 
Listing 24.1: Laboratory – Biochemistry 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 44 of 59 
Listing 24.2: Biochemistry (Abnormal only) 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 45 of 59 
Listing 25.1: Lymphocyte phenotype 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 46 of 59 
Listing 25.2: Thymopoieisis 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
Subject 
Number Visit 
Date of 
Collection 
(YYYY-MM-DD) 
Time of 
Collection 
(HH:MM) Variable 
Result 
Unit 
LLN 
ULN 
Flag* 
Comment 
 
 
xx-xxxxxx Infusion (Day 0) 
YYYY-MM-DD 
HH:MM 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
LLN=Lower Limit of Normal; ULN=Upper Limit of Normal 
* Flag: H=High, L=Low 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
Programming Note: Repeat this listing for: 
25.3 
Laboratory – Inflammation 
25.4 
Laboratory – Maturation 
CCI
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 47 of 59 
Listing 25.3: Inflammation 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 48 of 59 
Listing 25.4: Maturation 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 49 of 59 
Listing 26: Laboratory – HIV-1 RNA 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
 
 
Roche Assay 
 
 
 
Abbott Assay 
 
Subject 
Number 
Visit 
Date of 
Collection 
(YYYY-MM-DD) 
Result 
(Copies/mL) 
Flag* 
 
Date of 
Collection 
(YYYY-MM-DD) 
Result 
(Copies/mL) 
Flag* Comments 
 
 
 
 
 
xx-xxxxxx 
Screening 1 
YYYY-MM-DD 
xxxxxxxx 
Indeterminate 
YYYY-MM-DD 
xxxxxxxx 
- 
XXXXXXXXXXXXXXXXXXX 
Screening 2 
YYYY-MM-DD 
xxxxxxxx 
Indeterminate 
YYYY-MM-DD 
xxxxxxxx 
- 
XXXXXXXXXXXXXXXXXXX 
CD4+ Apheresis 
YYYY-MM-DD 
xxxxxxxx 
Indeterminate 
- 
- 
- 
G-CSF 1 
YYYY-MM-DD 
xxxxxxxx 
Indeterminate 
- 
- 
- 
Infusion (Day 0) 
YYYY-MM-DD 
xxxxxxxx 
Indeterminate 
YYYY-MM-DD 
xxxxxxxx 
- 
XXXXXXXXXXXXXXXXXXX 
Week 1 
YYYY-MM-DD 
xxxxxxxx 
Indeterminate 
- 
- 
- 
Week 2 
YYYY-MM-DD 
xxxxxxxx 
Indeterminate 
- 
- 
- 
 
 
 
 
 
* Flag: H=High, L=Low 
 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 50 of 59 
Listing 27.1: Vital Signs 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
Subject 
Number Visit 
Date Performed 
(YYYY-MM-DD) 
Time 
Performed 
(HH:MM) 
Time Point 
Weight (kg) 
Systolic Blood 
Pressure 
(mmHg) 
Diastolic Blood 
Pressure 
(mmHg) 
Pulse Rate 
(beats/min) 
Temperature 
(°C) 
Oxygen 
Saturation 
(%) 
 
 
 
 
 
 
 
 
 
xx-xxxxxx Screening 1 
YYYY-MM-DD 
HH:MM 
 
xx.x 
xxx 
xx 
xx 
xxL 
- 
CD4+ Apheresis 
YYYY-MM-DD 
HH:MM 
 
 
xxx 
xx 
xxL 
xx.x 
xx 
G-CSF 1 
YYYY-MM-DD 
HH:MM 
 
 
xxx 
xx 
xxL 
xx.x 
xx 
G-CSF 5 CD34+ Apheresis 
YYYY-MM-DD 
HH:MM 
 
 
xxx 
xx 
xxL 
xx.x 
xx 
 
 
 
 
 
 
 
 
 
Infusion (Day 0) 
YYYY-MM-DD 
HH:MM 
Pre 
 
xxx 
xx 
xxL 
xxL 
xx 
 
HH:MM 
T1 
 
xxx 
xx 
 
 
 
 
HH:MM 
T3 
 
xxx 
xx 
 
 
 
 
HH:MM 
T5 
 
xxx 
xx 
 
 
 
 
HH:MM 
T7 
 
xxx 
xx 
 
 
 
 
HH:MM 
H1 
 
xxx 
xx 
 
 
 
 
HH:MM 
H2 
 
xxx 
xx 
 
 
 
; 
 
HH:MM 
H3 
 
xxx 
xx 
 
 
 
 
HH:MM 
H4 
 
xxx 
xx 
 
 
 
 
HH:MM 
H5 
 
xxx 
xx 
 
 
 
YYYY-MM-DD 
HH:MM 
H6 
 
xxx 
xxH 
xx 
xx.x 
xx 
YYYY-MM-DD 
HH:MM 
H7 
 
xxx 
xxH 
xx 
xx.x 
xx 
YYYY-MM-DD 
HH:MM 
H8 
 
xxx 
xx 
xx 
xxL 
xx 
YYYY-MM-DD 
HH:MM 
H9 
 
xxx 
xx 
xx 
xxL 
xx 
YYYY-MM-DD 
HH:MM 
H10 
 
xxx 
xx 
xx 
xxL 
xx 
 
 
 
 
 
 
 
 
 
Week 1 
YYYY-MM-DD 
HH:MM 
 
 
xxx 
xxH 
xx 
xxL 
xx 
Week 2 
YYYY-MM-DD 
HH:MM 
 
 
xxx 
xx 
xx 
xx 
xx 
Week 4 
YYYY-MM-DD 
HH:MM 
 
 
xxx 
xx 
xx 
xx 
xx 
Week 6 
YYYY-MM-DD 
HH:MM 
 
 
xxx 
xx 
xx 
xx 
xx 
Week 8 
YYYY-MM-DD 
HH:MM 
 
 
xxx 
xx 
xx 
xx 
xx 
Week 12 
YYYY-MM-DD 
HH:MM 
 
 
xxx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
Flag: H=High, L=Low 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
Programming Note: Repeat this listing for: 
27.2 
Abnormal Vital Signs 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 51 of 59 
Listing 27.2: Abnormal Vital Signs 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 52 of 59 
Listing 28.1: Physical Examination 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
Subject Number 
Visit 
Date of 
Examination 
(YYYY-MM-DD) 
System 
Abnormal; 
specify 
Clinically 
Significant? 
 
 
xx-xxxxxx 
Screening 1 
YYYY-MM-DD 
General Appearance  
 
 
Dermatologic  
 
 
Hematologic  
 
 
HEENT n 
 
 
Respiratory  
 
 
Cardiovascular n 
 
 
Musculoskeletal n 
 
 
Gastrointestinal n 
skin rash resolved 
No 
 
Pelvic/Genitourinary  
 
 
Anal/Rectal nk 
 
 
Detailed Neurologic 
 
 
General Appearance  
 
 
Dermatologic  
 
 
Other 
xxxxxxxxxxxxxxxxxxxxxx 
No 
 
 
G-CSF 1 
YYYY-MM-DD 
General Appearance 
 
 
 
Infusion (Day 0) 
YYYY-MM-DD 
General Appearance 
 
 
 
Week 1 
YYYY-MM-DD 
General Appearance 
 
 
 
Week 2 
YYYY-MM-DD 
General Appearance 
 
 
 
Week 4 
YYYY-MM-DD 
General Appearance 
 
 
 
Week 6 
YYYY-MM-DD 
General Appearance 
 
 
 
HEENT: Head Eyes Ears Nose Throat 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
Programming Note: Repeat this listing for: 
28.2 
Abnormal Physical Examination 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 53 of 59 
Listing 28.2: Abnormal: Physical Examination 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 54 of 59 
Listing 29.1: Cal-1 Integration Analysis 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
Subject Number 
Visit 
Collection Date 
(YYYY-MM-DD) 
Analysis Performed? * 
Are there any CS abnormalities on PE 
or CBC/diff? (mono-clonality) 
 
xx-xxxxxx 
Infusion (Day 0) 
YYYY-MM-DD 
Not Required 
Week 12 
YYYY-MM-DD 
Not done (Cal-1 Marking – PB <1%) 
Week 24 
YYYY-MM-DD 
Not done (Cal-1 Marking – PB <1%) 
Week 48 
YYYY-MM-DD 
Not done (Cal-1 Marking – PB <1%) 
 
xx-xxxxxx 
Infusion (Day 0) 
YYYY-MM-DD 
Not Required 
Week 12 
YYYY-MM-DD 
Not done (Cal-1 Marking – PB <1%) 
Week 24 
YYYY-MM-DD 
Not done (Cal-1 Marking – PB <1%) 
Week 48 
YYYY-MM-DD 
Not done (Cal-1 Marking – PB <1%) 
 
xx-xxxxxx 
Infusion (Day 0) 
YYYY-MM-DD 
Not Required 
Week 12 
YYYY-MM-DD 
Not done (Cal-1 Marking – PB <1%) 
Week 24 
YYYY-MM-DD 
Not done (Cal-1 Marking – PB <1%) 
Week 48 
YYYY-MM-DD 
Not done (Cal-1 Marking – PB <1%) 
 
xx-xxxxxx 
Infusion (Day 0) 
YYYY-MM-DD 
Not Required 
Week 12 
YYYY-MM-DD 
Not done (Cal-1 Marking – PB <1%) 
Week 24 
YYYY-MM-DD 
Not done (Cal-1 Marking – PB <1%) 
Week 48 
YYYY-MM-DD 
Not done (Cal-1 Marking – PB <1%) 
Early discontinuation / 
withdrawal 
YYYY-MM-DD 
Not done (Cal-1 Marking – PB <1%) 
 
* Integration analysis performed only when Cal-1 Marking is >= 1%; 
Not done (Cal-1 Marking – PB<1%); No predominant clone detected; Predominant mono-clonality detected or Predominant oligo-clonality 
detected; 
If predominant clone detected, batch analysis of previous samples (‘Baseline’ or ‘Not done’ due to <1% marking) will be performed. 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 55 of 59 
Listing 29.2: Cal-1 Integration Analysis (Re-test) 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
Subject 
Number 
Visit 
Predominant mono-clonality confirmed 
Predominant oligo-clonality confirmed 
Retest Date 
(YYYY-MM-DD) 
Sequencing 
performed 
Prominent 
integration site 
location 
Are there any CS 
abnormalities on PE or 
CBC/diff? (mono-clonality) 
Retest Date 
(YYYY-MM-DD) 
Sequencing 
performed 
Prominent 
integration site 
location 
Clustering detected/ 
Site 
 
xx-xxxxxx 
Infusion (Day 0) 
YYYY-MM-DD 
Yes 
xxxxxxxxxxxxx 
 
YYYY-MM-DD 
 
xxxxxxxxxxxxx 
Yes – xxxxxxxxxxx 
Week 12 
YYYY-MM-DD 
No 
xxxxxxxxxxxxx 
 
YYYY-MM-DD 
 
xxxxxxxxxxxxx 
No 
Week 24 
YYYY-MM-DD 
Yes 
xxxxxxxxxxxxx 
 
YYYY-MM-DD 
 
xxxxxxxxxxxxx 
No 
Week 48 
YYYY-MM-DD 
Yes 
xxxxxxxxxxxxx 
 
YYYY-MM-DD 
 
xxxxxxxxxxxxx 
No 
 
 
 
 
 
 
 
 
xx-xxxxxx 
Infusion (Day 0) 
YYYY-MM-DD 
Yes 
xxxxxxxxxxxxx 
 
YYYY-MM-DD 
 
xxxxxxxxxxxxx 
No 
Week 12 
YYYY-MM-DD 
No 
xxxxxxxxxxxxx 
 
YYYY-MM-DD 
 
xxxxxxxxxxxxx 
No 
Week 24 
YYYY-MM-DD 
Yes 
xxxxxxxxxxxxx 
 
YYYY-MM-DD 
 
xxxxxxxxxxxxx 
No 
Week 48 
YYYY-MM-DD 
Yes 
xxxxxxxxxxxxx 
 
YYYY-MM-DD 
 
xxxxxxxxxxxxx 
No 
 
 
 
 
 
 
 
 
xx-xxxxxx 
Infusion (Day 0) 
YYYY-MM-DD 
Yes 
xxxxxxxxxxxxx 
 
YYYY-MM-DD 
 
xxxxxxxxxxxxx 
No 
Week 12 
YYYY-MM-DD 
No 
xxxxxxxxxxxxx 
 
YYYY-MM-DD 
 
xxxxxxxxxxxxx 
No 
Week 24 
YYYY-MM-DD 
Yes 
xxxxxxxxxxxxx 
 
YYYY-MM-DD 
 
xxxxxxxxxxxxx 
No 
Week 48 
YYYY-MM-DD 
Yes 
xxxxxxxxxxxxx 
 
YYYY-MM-DD 
 
xxxxxxxxxxxxx 
No 
 
 
 
 
 
 
 
 
xx-xxxxxx 
Infusion (Day 0) 
YYYY-MM-DD 
Yes 
xxxxxxxxxxxxx 
 
YYYY-MM-DD 
 
xxxxxxxxxxxxx 
 
Week 12 
YYYY-MM-DD 
No 
xxxxxxxxxxxxx 
 
YYYY-MM-DD 
 
xxxxxxxxxxxxx 
 
Week 24 
YYYY-MM-DD 
Yes 
xxxxxxxxxxxxx 
 
YYYY-MM-DD 
 
xxxxxxxxxxxxx 
 
Week 48 
YYYY-MM-DD 
Yes 
xxxxxxxxxxxxx 
 
YYYY-MM-DD 
 
xxxxxxxxxxxxx 
 
Early 
discontinuation / 
withdrawal 
YYYY-MM-DD 
Yes 
xxxxxxxxxxxxx 
 
YYYY-MM-DD 
 
xxxxxxxxxxxxx 
 
 
,QWHJUDWLRQDQDO\VLVSHUIRUPHGRQO\ZKHQ&DO0DUNLQJLV! 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 56 of 59 
Listing 30: Replication Competent Lentivirus (RCL) 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
Subject 
Number 
Visit 
Collection Date 
(YYYY-MM-DD) 
VSV-G PCR Signal * 
Number of 
copies of VSV-G 
DNA ** 
Retest Sample 
Collection 
Date 
(YYYY-MM-DD) 
Positive 
VSV-G PCR 
Signal 
Confirmed? 
Number of 
copies of VSV-G 
DNA *** 
AE# for Positive 
VSV-G PCR Signal 
 
 
 
 
 
 
 
xx-xxxxxx 
Infusion (Day 0) 
YYYY-MM-DD 
Negative 
- 
- 
- 
- 
 
Week 12 
YYYY-MM-DD 
Negative 
- 
- 
- 
- 
 
Week 24 
YYYY-MM-DD 
Negative 
- 
- 
- 
- 
 
Week 48 
YYYY-MM-DD 
Negative 
- 
- 
- 
- 
 
 
 
 
 
 
 
 
xx-xxxxxx 
Infusion (Day 0) 
YYYY-MM-DD 
Negative 
- 
- 
- 
- 
 
Week 12 
YYYY-MM-DD 
Negative 
- 
- 
- 
- 
 
Week 24 
YYYY-MM-DD 
Negative 
- 
- 
- 
- 
 
Week 48 
YYYY-MM-DD 
Negative 
- 
- 
- 
- 
 
 
 
 
 
 
 
 
xx-xxxxxx 
Infusion (Day 0) 
YYYY-MM-DD 
Negative 
- 
- 
- 
- 
 
Week 12 
YYYY-MM-DD 
Negative 
- 
- 
- 
- 
 
Week 24 
YYYY-MM-DD 
Negative 
- 
- 
- 
- 
 
Week 48 
YYYY-MM-DD 
Negative 
- 
- 
- 
- 
 
 
 
 
 
 
 
 
xx-xxxxxx 
Infusion (Day 0) 
YYYY-MM-DD 
Negative 
- 
- 
- 
- 
 
Week 12 
YYYY-MM-DD 
Negative 
- 
- 
- 
- 
 
Week 24 
YYYY-MM-DD 
Negative 
- 
- 
- 
- 
 
Week 48 
YYYY-MM-DD 
Negative 
- 
- 
- 
- 
 
 
 
 
 
 
 
 
* VSV-G PCR Signal: indicated by a blank when results are pending. 
** Number of VSV-G DNA copies per 0.2ug peripheral blood DNA 
*** Number of VSV-G DNA copies per 0.2ug peripheral blood DNA on re-test samples 
 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 57 of 59 
Listing 31: HIV-1 Tropism Assay 
Protocol: CAL-USA-11 
Population: All Enrolled 
 
Cohort: Cohort 1 
 
Subject Number 
Visit 
Collection Date/Time 
(YYYY-MM-DD) 
Result * 
Clinical Significant 
Comment 
 
 
 
xx-xxxxxx 
Screening 1 
YYYY-MM-DD/ HH:MM 
r5 
No 
xxxxxxxxxx 
Week 12 
YYYY-MM-DD/ HH:MM 
r5 
No 
xxxxxxxxxx 
Week 48 
YYYY-MM-DD/ HH:MM 
unreportable 
No 
xxxxxxxxxx 
 
 
 
xx-xxxxxx 
Screening 1 
YYYY-MM-DD/ HH:MM 
R5 
No 
xxxxxxxxxx 
Week 12 
YYYY-MM-DD/ HH:MM 
R5 
No 
xxxxxxxxxx 
 
 
 
xx-xxxxxx 
Screening 1 
YYYY-MM-DD/ HH:MM 
r5 
No 
xxxxxxxxxx 
Week 12 
YYYY-MM-DD/ HH:MM 
r5 
No 
xxxxxxxxxx 
Week 48 
YYYY-MM-DD/ HH:MM 
r5 
No 
xxxxxxxxxx 
 
 
 
xx-xxxxxx 
Screening 1 
YYYY-MM-DD/ HH:MM 
r5 
No 
xxxxxxxxxx 
Week 24 
YYYY-MM-DD/ HH:MM 
r5 
No 
xxxxxxxxxx 
 
 
 
xx-xxxxxx 
Screening 1 
YYYY-MM-DD/ HH:MM 
r5 
No 
xxxxxxxxxx 
Week 12 
YYYY-MM-DD/ HH:MM 
r5 
No 
xxxxxxxxxx 
 
 
 
xx-xxxxxx 
Screening 1 
YYYY-MM-DD/ HH:MM 
R5 
No 
xxxxxxxxxx 
Week 12 
YYYY-MM-DD/ HH:MM 
R5 
No 
xxxxxxxxxx 
 
 
 
xx-xxxxxx 
Screening 1 
YYYY-MM-DD/ HH:MM 
r5 
No 
xxxxxxxxxx 
xx-xxxxxx 
Screening 1 
YYYY-MM-DD/ HH:MM 
r5 
No 
xxxxxxxxxx 
 
 
 
* Results: CCR5 (R5), CXCR4 (X4) or dual mixed (R5/X4) 
 
 
 
 
 
Clinical cut-off date: DDMMMYYYY                                                                                                      
Program: filepath_name, Output: filepath_name   Created: DDMMMYYYY HH:MM  
 
 
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 58 of 59 
Listing 32.1: C46 Immunogenicity – Humoral Response 
Protocol: CAL-USA-11 
Population: All Enrolled 
CCI
CCI


Protocol No: CAL-USA-11  
Document status: Mock Listings, Final, V1.0  
15 December 2017  
 Strictly Confidential 
 
Page 59 of 59 
Listing 32.2: C46 Immunogenicity – Cellular Response 
Protocol: CAL-USA-11 
Population: All Enrolled 
CCI
CCI