Clinical trial NCT02707861
Conditions: HIV
Keywords: HIV Resistant Salvage ibalizumab antibody AIDS
Sponsor: TaiMed Biologics Inc.
Start date: 2016-03-01; Completion date: 2018-11-01
Enrollment: 79 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Ibalizumab is a monoclonal antibody that works by blocking HIV entry into the immune system cells (CD4+ or T-cells) the virus typically infects. Ibalizumab is intended for use in combination with other anti-HIV drugs in people with multi-drug resistant HIV and limited treatment options. This study will collect further information on the safety and tolerability of intravenously administered (IV) ibalizumab combined with an optimized background regimen for treating multi-drug resistant HIV-1 infection, and will provide continuing access to ibalizumab for patients completing a prior ibalizumab clinical trial.

Detailed description:
Participants will enroll into one of two study cohorts. Cohort 1 will provide continued administration of IV ibalizumab for patients completing a prior ibalizumab clinical trial (TaiMed-sponsored or Investigator-Sponsored). Patients will continue to receive IV infusions of ibalizumab at the dosage assigned in the previous study - either 800 mg once every two weeks, or 2000 mg once every four weeks.

Cohort 2 will provide IV ibalizumab, 800 mg once every two weeks, for qualifying patients with multi-drug resistant HIV-1 and limited treatment options who have never previously received ibalizumab.

Participants may continue in this study for 48 weeks, or until ibalizumab becomes commercially available, whichever occurs first.

Arms: arm 1: IV ibalizumab (combined with optimized background regimen):

800 mg once every two weeks for patients receiving that dosage on prior, successfully completed ibalizumab clinical trial

OR

2000 mg once every four weeks for patients receiving that dosage on prior, successfully completed ibalizumab clinical trial

Administered for 48 weeks, or until ibalizumab becomes commercially available arm 2: IV ibalizumab (combined with optimized background regimen):

800 mg once every two weeks for qualifying patients who have never received ibalizumab

Administered for 48 weeks, or until ibalizumab becomes commercially available
Interventions: intervention 1: ibalizumab intervention 2: Optimized Background Regimen
Intervention descriptions: intervention 1: Intravenous infusion of humanized monoclonal antibody binding with a region of Domain 2 of CD4 receptor, blocking post-attachment conformational changes necessary for HIV cell entry intervention 2: An investigator-selected, standard-of-care combination regimen of antiretroviral agents for treating HIV-1 infection, selected based upon patient treatment history and the results of previous viral resistance testing. The combination must contain at least one agent other than ibalizumab to which the patient's virus is sensitive (susceptible).

Protocol documents:
Prot_000.pdf: 
TAIMED BIOLOGICS, INC. 
CONFIDENTIAL 
PROTOCOL: TMB-311 
DATE: 11 DECEMBER 2017 
 
 
 
 
 
STUDY PROTOCOL 
 
 
 
A Phase 3, Multicenter, Expanded Access Study of Ibalizumab Plus an Optimized 
Background Regimen (OBR) in Treatment-Experienced Patients Infected With Multi-Drug 
Resistant (MDR) HIV-1 
 
PROTOCOL NUMBER: TMB-311 
NCT02707861 
 
 
Version: 
1.3 
Date of Protocol: 
11 December  2017 
 
Sponsor: 
TaiMed Biologics, Inc. 
2 Executive Circle, Suite 280 
Irvine, CA 92614 


TAIMED BIOLOGICS, INC. 
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Sponsor Contact: 
TaiMed Biologics, Inc. 
2 Executive Circle, Suite 280 
Irvine, CA 92614 
Project Manager: 
 
Christine Anderson, PhD 
Westat 
1600 Research Blvd. 
Rockville, MD 20850 
Phone: 713-353-7911 
 
Primary Contact: 
Stanley Lewis, MD MPH 
Vice-President and Chief Medical Officer 
2 Executive Circle, Suite 280 
Irvine, CA 92614 
Phone: 713-252-2619 
Medical Monitor: 
Stanley Lewis, MD MPH 
Vice-President and Chief Medical Officer 
2 Executive Circle, Suite 280 
Irvine, CA 92614 
Phone: 713-252-2619 
Serious Adverse 
Event Reporting: 
Westat 
1600 Research Blvd. 
Rockville, MD 20850 
Phone: 888-464-5246 
Fax: 888-865-1983 
Email: Regulatory@Westat.com 
 
Proprietary Notice: 
This document contains mainly unpublished data and is the sole 
property of TaiMed Biologics, Inc. Therefore, it is provided to you in 
strict confidence as an investigator, potential investigator, or consultant. 
The information may be reviewed by you, your staff, and your 
institutional review board/independent ethics committee. It is 
understood that this information will not be disclosed to others without 
written authorization from TaiMed Biologics, Inc., except to the extent 
necessary to obtain informed consent from those persons to whom the 
drug may be administered. 
 
Ethics Statement: 
The study will be completed according to the International Conference 
on Harmonisation guidelines E6(R1): Good Clinical Practice: 
Consolidated Guideline and E2A: Clinical Safety Data Management. 
Compliance with this standard provides public assurance that the rights, 
safety, and well-being of trial patients are protected, consistent with the 
principles that have their origin in the Declaration of Helsinki. The 
study will also follow the standards set forth in the Code of Federal 
Regulations Title 21 Parts 11 (Electronic Records), 50 (Protection of 


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Human Subjects), 54 (Financial Disclosure by Clinical Investigators), 56 
(Institutional Review Boards), and 312 (Investigational New Drug 
Application).  
 
 


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DATE: 11 DECEMBER 2017 
 
 
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Table of Contents 
 
 
PROTOCOL SUMMARY ..................................................................................................... 1 
ABBREVIATIONS ................................................................................................................. 7 
1. Introduction .......................................................................................................................... 9 
1.1 
Background ............................................................................................ 9 
1.2 
Clinical Studies ...................................................................................... 9 
1.3 
Pharmacokinetic Profile .................................................................... 15 
2. Study Objectives ................................................................................................................. 16 
2.1 
Primary Objectives ............................................................................. 16 
2.2 
Secondary Objectives ......................................................................... 16 
3. Study Plan ............................................................................................................................ 17 
3.1 
Overall Design .................................................................................... 17 
3.2 
Discussion of Trial Design ............................................................... 18 
3.3 
Dose Selection .................................................................................... 19 
3.4 
Schedule of Events ............................................................................. 19 
3.5 
Effectiveness Assessments................................................................ 44 
3.6 
Safety Assessments ............................................................................. 44 
4. Study Treatments ............................................................................................................... 45 
4.1 
Study Drug Dosage and Administration ........................................ 45 
4.1.1 
Cohort 1 .............................................................................. 45 
4.1.2 
Cohort 2 .............................................................................. 46 
4.1.3 
Administration .................................................................... 47 
4.2 
Prohibited Medications and Restrictions........................................ 47 
4.3 
Measurement of Patient Adherence ................................................ 49 
4.4 
Missed Doses of Study Drug ............................................................ 49 
4.4.1 
Cohort 1 .............................................................................. 49 
4.4.2 
Cohort 2 .............................................................................. 50 
4.5 
Study Drug Description .................................................................... 51 
4.6 
Study Drug Packaging, Storage, and Disposal ............................... 51 
4.7 
Study Drug Accountability................................................................ 52 
5. Patient Enrollment ............................................................................................................. 53 
5.1 
Inclusion Criteria ................................................................................ 53 
5.2 
Exclusion Criteria ............................................................................... 54 
5.3 
Patient Withdrawal and Discontinuation ....................................... 56 
5.3.1 
Reasons for Withdrawal .................................................... 56 
5.3.2 
Handling Withdrawals and Discontinuations ............... 57 
5.3.3 
Sponsor or Regulatory Agency Termination of 
Study ..................................................................................... 57 
6. Study Visits .......................................................................................................................... 58 
6.1 
Cohort 1: 800 mg Every 2 Weeks .................................................... 58 
6.1.1 
Screening/Day 0 ................................................................ 58 
6.1.2 
Events for Day 14 (±1 day) and Weeks 4, 6, 8, 
10, 14, 16, 18, 20, 22, 26, 28, 30, 32, 34, 38, 40, 
42, 44, 46, 50, 52, 54, 56, 58, 62, 64, 66, 68, 70, 


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74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 98, 100, 
102, 104, 106, 110, 112, 114, 116, 118, 122, 124, 
126, 128, 130, 134, 136, 138, 140, and 142 (±2 
days)...................................................................................... 60 
6.1.3 
Events for Weeks 12, 24, 36, 48, 60, 72, 96, 108, 
120, 132, 144/EOS and 150/Follow-up (±2 
days)...................................................................................... 60 
6.2 
Cohort 1: 2,000 mg Every 4 Weeks................................................. 61 
6.2.1 
Screening/Day 0 ................................................................ 62 
6.2.2 
Events for Weeks 4, 8, 16, 20, 28, 32, 40, 44, 52, 
56, 64, 68, 76, 80, 84, 88, 92, 100, 104, 112, 116, 
124, 128, 136, and 140 (±2 days)..................................... 64 
6.2.3 
Events for Weeks 12, 24, 36, 48, 60, 72, 96, 108, 
120, 132, , 144/EOS, and 150/Follow-up (±2 
days)...................................................................................... 64 
6.3 
Cohort 2 ............................................................................................... 65 
6.3.1 
Screening (Weeks -6 to -1) ............................................... 66 
6.3.2 
Day 0/Baseline ................................................................... 67 
6.3.3 
Events for Day 7 (±1 day) ............................................... 68 
6.3.4 
Events for Day 14 (±1 day), and Weeks 4, 6, 8, 
10, 14, 16, 18, 20, 22, 26, 30, 32, 34, 38, 40, 42, 
44, 46, 50, 52, 54, 56, 58, 62, 64, 66, 68, 70, 74, 
76, 78, 80, 82, 86, 88, 90, 92, 94, 98, 100, 102, 
104, 106, 110, 112, 114, 116, 118, 122, 124, 126, 
128, 130, 134, 136, 138, 140, and 142 (±2 days)........... 69 
6.3.5 
Events for Weeks 12, 24, 48, 60, 72, 84, 96, 108, 
120, 132, and 144/EOS (±2 days) .................................. 70 
6.3.6 
Events for Weeks 28 and 36 (±2 days) .......................... 71 
6.3.7 
Events for Week 150/Follow-up Visit (±2 days) 
(Study drug is not administered at this visit) ................. 71 
6.4 
Early Withdrawal Procedures ........................................................... 72 
6.5 
Unscheduled Visits ............................................................................. 73 
7. Study Assessments ............................................................................................................. 74 
7.1 
Activities to Be Completed ............................................................... 74 
7.1.1 
Demographic Data, Medical History, and 
Concomitant Medications ................................................ 74 
7.1.2 
Complete Physical Examination ..................................... 74 
7.1.3 
Abbreviated Physical Examination ................................. 75 
7.1.4 
Vital Sign Measurements .................................................. 75 
7.2 
Blood and Urine Samples .................................................................. 75 
7.2.1 
Hepatitis Serology and C-Reactive Protein ................... 75 
7.2.2 
Clinical Laboratory Parameters ....................................... 75 
7.2.3 
Archive Sample .................................................................. 76 
7.2.4 
Serum Follicle-Stimulating Hormone Testing .............. 77 
7.2.5 
Pregnancy Testing .............................................................. 77 
7.2.6 
HIV-1 RNA Level ............................................................. 77 


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7.2.7 
HIV-1 Viral Resistance Testing ....................................... 77 
7.2.8 
CD4+ Cell Count ................................................................ 78 
7.2.9 
Immunogenicity of Ibalizumab ....................................... 78 
8. Adverse Events ................................................................................................................... 78 
8.1 
Definitions ........................................................................................... 78 
8.2 
Eliciting Adverse Event Information.............................................. 79 
8.3 
Reporting Adverse Events ................................................................ 80 
8.4 
Assessment of Causality .................................................................... 81 
8.5 
Assessment of Severity ...................................................................... 82 
8.6 
Serious Adverse Event Reporting ................................................... 83 
8.7 
Pregnancy ............................................................................................. 85 
9. Statistical Considerations .................................................................................................. 87 
9.1 
General Methodology ........................................................................ 87 
9.2 
Populations for Analysis.................................................................... 87 
9.2.1 
Efficacy Populations.......................................................... 87 
9.2.2 
Safety Population ............................................................... 88 
9.3 
Patient Disposition ............................................................................. 88 
9.4 
Definition of Baseline ........................................................................ 88 
9.5 
Demographics and Baseline Characteristics .................................. 89 
9.6 
Exposure to Study Medication ......................................................... 89 
9.7 
Safety Analyses .................................................................................... 89 
9.7.1 
Adverse Events .................................................................. 89 
9.7.2 
Clinical Safety Laboratory Parameters ........................... 89 
9.8 
Efficacy ................................................................................................. 90 
10. Data Handling and Quality Assurance ......................................................................... 90 
10.1 
Electronic Case Report Forms ......................................................... 90 
10.2 
Monitoring of the Study .................................................................... 91 
10.3 
Inspection of Records........................................................................ 92 
10.4 
Study Record Retention .................................................................... 92 
11. Administrative Considerations ...................................................................................... 93 
11.1 
Confidentiality ..................................................................................... 93 
11.2 
Institutional Review Board or Independent Ethics 
Committee Approval ......................................................................... 93 
11.3 
Modification of the Protocol ............................................................ 94 
11.4 
Informed Consent .............................................................................. 94 
11.5 
Protocol Violations and Deviations ................................................ 95 
11.6 
Study Reporting Requirements ........................................................ 96 
11.7 
Financial Disclosure and Obligations ............................................. 96 
11.8 
Investigator Documentation............................................................. 97 
11.9 
Study Conduct ..................................................................................... 97 
11.10 Publications ......................................................................................... 98 
 
References .......................................................................................................... 99 
 
 
 


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Appendices 
Appendices to this protocol are presented in a separate document titled: 
“Appendices to Protocol TMB-311: A Phase 3, Single Arm, Multicenter, Expanded Access Study of 
Ibalizumab Plus an Optimized Background Regimen (OBR) in Treatment-Experienced Patients 
Infected With Multi-Drug Resistant (MDR) HIV-1” 
 
The Appendices include the following: 
 
Appendix A: CDC Classification System for HIV Infection 
Appendix B: Division of AIDS: Table for Grading the Severity of Adult and Pediatric 
Adverse Events Version 2.0, November 2014 
Appendix C: “The diagnosis and management of anaphylaxis: An updated practice 
parameter” 
 


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PROTOCOL SUMMARY 
 
Protocol Number: 
TMB-311 
Title: 
A Phase 3, Multicenter, Expanded Access Study of Ibalizumab Plus an 
Optimized Background Regimen (OBR) in Treatment-Experienced 
Patients Infected With Multi-Drug-Resistant (MDR) HIV-1  
Sponsor: 
TaiMed Biologics, Inc. 
2 Executive Circle, Suite 280 
Irvine, CA 92614 
Study Phase: 
3 
Patients and 
Investigator Sites:  
Anticipated enrollment is approximately 100 patients from 
approximately 40 sites in North America and the European Union; 
however, the numbers of participating patients will not be limited and 
may exceed 100 and the number of sites will not be limited and may 
exceed 40. 
Study Drug Dosage 
and Route of 
Administration: 
The investigational product, ibalizumab, is a humanized IgG4 
monoclonal antibody (MAb) administered via intravenous infusion (IV). 
Patients will be enrolled in one of two Cohorts (Cohort 1 and Cohort 
2). Cohort 1 patients will continue their current dosage of ibalizumab 
(800 mg every 2 weeks or 2,000 mg every 4 weeks). Cohort 2 patients 
will receive a 2,000 mg loading dose at Baseline/Day 0 followed by 800 
mg maintenance doses every 2 weeks. 
All patients will receive an OBR, which is a standard-of-care regimen 
selected by the investigator based on treatment history and the results of 
viral resistance testing.  
Control Drug, Dosage, 
and Route of 
Administration: 
None  
Objectives: 
 
The primary objectives of this study are to: 
 
Cohort 1 
◼ 
Continue to provide ibalizumab to patients currently receiving 
ibalizumab treatment under Investigator-sponsored INDs or 
TaiMed-sponsored protocols 
◼ 
Demonstrate the safety and tolerability of ibalizumab in human 
immunodeficiency virus (HIV)-positive patients with MDR HIV 
infection 
Cohort 2 
◼ 
Provide access to ibalizumab for qualifying MDR HIV-1-infected 
patients with limited treatment options 
◼ 
Demonstrate the safety and tolerability of ibalizumab in HIV-


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positive patients with MDR HIV infection 
The secondary objectives of this study are to: 
 
◼ 
Demonstrate the antiviral activity of ibalizumab in HIV-positive 
patients with MDR HIV infection 
◼ 
Characterize HIV-1 sensitivity/susceptibility changes associated 
with protocol-defined virologic failure after ibalizumab 
administration in combination with the OBR 
◼ 
Determine the presence and significance of anti-ibalizumab 
antibodies associated with protocol-defined virologic failure after 
ibalizumab administration, if any (immunogenicity of ibalizumab) 
Patient Population: 
Inclusion Criteria 
 
Patients will be enrolled in one of two Cohorts (Cohort 1 and    Cohort 
2)   
 
Patients may be enrolled in Cohort 1 if they meet both of the following 
criteria: 
 
1. Are currently receiving ibalizumab via other TaiMed-sponsored or 
Investigator-sponsored IND protocol 
2. Are capable of understanding and have voluntarily signed the 
informed consent document 
 
Patients may be enrolled in Cohort 2 if they meet all of the following 
criteria: 
 
1. Are 18 years of age or older 
2. Are capable of understanding and have voluntarily signed the 
informed consent document 
3. Have documented HIV-1 infection by official, signed, written 
history (e.g., laboratory report); otherwise, an HIV-antibody test will 
be performed 
4. Are able and willing to comply with all protocol requirements and 
procedures 
5. Have a viral load >1,000 copies/mL and documented resistance to 
at least one antiretroviral medication from each of three classes of 
antiretroviral medications as measured by previous viral resistance 
testing (resistance testing is not provided by the study for 
qualification purposes) 
6. Have a history of at least 6 months on antiretroviral treatment 
7. Are receiving a failing antiretroviral regimen OR have failed and are 
off therapy  


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8. Have viral sensitivity/susceptibility to at least one antiretroviral 
agent other than ibalizumab, as determined by a previous resistance 
test performed within 6 months of Screening, and be willing and 
able to be treated with at least one agent to which the patient’s viral 
isolate is fully sensitive/susceptible according to the Screening 
resistance tests as a component of the OBR 
9. If sexually active, are willing to use an effective method of 
contraception during the study and for 30 days after the last 
administration of the study drug 
Patient Population: 
Exclusion Criteria 
 
There are no Exclusion Criteria for patients meeting the Inclusion 
Criteria for Cohort 1. 
 
For Cohort 2, patients having or meeting any of the following 
conditions or characteristics will be excluded from the study: 
 
1. Eligible for participation in other TaiMed Biologics-sponsored 
clinical trials of ibalizumab 
2. Any significant diseases (other than HIV-1 infection) or clinically 
significant findings, including psychiatric and behavioral problems, 
determined from Screening, medical history, and/or physical 
examination that, in the investigator’s opinion, would preclude the 
patient from participating in the study 
3. Any significant acute illness within 1 week before the first 
administration of investigational medication on the study 
4. Any active infection secondary to HIV requiring acute therapy; 
however, patients who require maintenance therapy (i.e., secondary 
prophylaxis for opportunistic infections) will be eligible for the 
study. 
5. Any immunomodulating therapy (including interferon), systemic 
steroids, or systemic chemotherapy within 4 weeks before Day 0 
6. Any prior exposure to ibalizumab (formerly TNX-355 and Hu5A8) 
7. Any vaccination within 7 days before Day 0 
8. Any female patient who is pregnant, intends to become pregnant, or 
is currently breastfeeding 
9. Any current alcohol or illicit drug use that, in the investigator’s 
opinion, will interfere with the patient’s ability to comply with the 
study schedule and protocol evaluations 
10. Any previous clinically significant allergy or hypersensitivity to any 
excipient in the ibalizumab formulation 
11. Any radiation therapy during the 28 days before first administration 
of investigational medication on this study 


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12. Any clinically significant Grade 3 or 4 laboratory abnormality 
according to the Division of AIDS (DAIDS) grading scale, except 
for the following asymptomatic Grade 3 events: 
➢ triglyceride elevation 
➢ total cholesterol elevation 
Study Design: 
 
This Phase 3, multicenter, expanded access study will evaluate the safety 
and tolerability of ibalizumab in treatment-experienced patients infected 
with MDR HIV-1. Patients will be enrolled in one of two Cohorts 
(Cohort 1 and Cohort 2): 
Cohort 1 (continuing treatment) 
◼ 
Patients will continue on an ibalizumab-containing regimen at 
their current dosage in combination with a current OBR.   
Cohort 2 (initiating ibalizumab) 
◼ 
On Day 0 patients will receive one 2,000 mg dose (loading dose) 
of ibalizumab. An OBR that is selected based on resistance test 
results and antiretroviral history will be initiated on Day 0 and 
must include at least one agent to which the patient’s virus is 
susceptible.  
◼ 
Beginning at Day 14, 800 mg of ibalizumab will be administered 
every 2 weeks through the remainder of the study. 
Virologic failure is defined as two consecutive measurements beginning 
at Week 24 or later if less than a 0.5 log10 decline in viral load from 
Baseline viral load. 
Patients may be discontinued from the study: 
▪ At the patient’s or investigator’s request 
▪ If the patient becomes pregnant 
▪ For protocol violation 
▪ For experiencing virologic failure 
▪ For treatment-related serious or intolerable adverse events (AEs) 
(DAIDS criteria, see Appendix B) 
▪ For toxicity (defined as two consecutive laboratory results, at 
least 14 days apart, with a CD4+ cell count below 200 cells/mm3 
that also represents a 50% reduction from the baseline CD4+ 
cell count) 
▪ Upon commercial availability of ibalizumab  


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Safety and 
Effectiveness 
Assessments: 
Primary safety and effectiveness variables: 
 
Cohort 1 and Cohort 2 
◼ 
Safety and tolerability of ibalizumab as assessed by AEs and 
Discontinuations 
 
Cohort 2 only 
◼ 
Proportion of patients achieving a ≥0.5 log10 decrease from 
Baseline in viral load at Day 7 
 
Secondary safety and effectiveness variables: 
 
Cohort 1 and Cohort 2 
◼ 
HIV-1 sensitivity/susceptibility changes associated with virologic 
failure after administration of ibalizumab 
 
Cohort 2 only 
◼ 
Proportion of patients with HIV-1 RNA levels <50 copies/mL 
and <400 copies/mL at assessment time points 
◼ 
Mean change from Baseline in viral load at Day 7 and all 
assessment time points 
◼ 
Proportion of patients achieving a ≥0.5 log10 and ≥1.0 log10 
decrease from Baseline in viral load at all assessment time points 
 
Safety Assessments: 
Safety assessments will include the following: 
◼ 
Physical examinations 
◼ 
Vital sign measurements 
◼ 
Clinical laboratory parameters (hematology, serum chemistry, and 
urinalysis) 
◼ 
Monitoring of AEs and concomitant medications 
◼ 
Incidence of Class C events as defined by the CDC Classification 
System for HIV Infection (Appendix A) 
◼ 
Anti-ibalizumab antibody levels (immunogenicity of ibalizumab)  


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Statistical 
Considerations: 
Sample Size: A sample size of approximately 100 patients is anticipated 
to be enrolled, though the number of participating patients will not be 
limited and may exceed 100. The analysis of study data will be primarily 
descriptive, with emphasis on tabular and graphical displays. Summary 
descriptive statistics will be calculated along with point and interval 
estimates of AEs. 
Effectiveness: (Cohort 2 only) The primary effectiveness endpoint of 
the study is the proportion of patients achieving a ≥0.5 log10 decrease 
from Baseline in viral load at Day 7. 
Safety Analyses: The safety analyses will include descriptions of 
treatment-emergent AEs (TEAEs), Class C events per the CDC 
Classification System for HIV Infection, clinical laboratory test results, 
physical examination findings, vital sign results, and immunogenicity of 
ibalizumab. 
 


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ABBREVIATIONS 
 
ABBREVIATION 
TERM 
 
 
AE 
adverse event 
AIDS 
acquired immunodeficiency syndrome 
ALT 
alanine aminotransferase  
ART 
antiretroviral therapy 
AST 
aspartate aminotransferase  
CD4 
glycoprotein expressed on the surface of T-helper cells 
CD4+ 
type of white blood cell, also called T-lymphocytes, T-cells, or T-helper cells 
CDC 
Centers for Disease Control and Prevention 
CFR 
Code of Federal Regulations 
cGMP 
current Good Manufacturing Practices 
CRF 
case report form 
CT 
computed tomography 
DAIDS 
Division of AIDS 
DSMB 
data and safety monitoring board 
EC 
ethics committee 
EDC 
electronic data capture 
ELISA 
enzyme-linked immunosorbent assay 
EOS 
end of study 
FDA 
Food and Drug Administration 
FSH 
follicle-stimulating hormone 
HAART 
highly active antiretroviral therapy  
HHS 
Department of Health and Human Services 
HIV-1 
human immunodeficiency virus type-1 
HTE 
heterogeneous treatment effect 
ICH 
International Conference on Harmonisation 
ID 
identification 
IND 
Investigational New Drug 
IRB 
institutional review board 
ITT 
intention-to-treat 
IV 
intravenous 
LLOQ 
lower limit of quantitation 
MAb 
monoclonal antibody 
MDR 
MEdDRA 
multi-drug resistant 
Medical Dictionary for Regulatory Activities  
MEF 
missing equals failure 
MESF 
molecules of equivalent soluble fluorescence 
mITT 
modified intention-to-treat 
Mu5A8 
murine progenitor of ibalizumab 
OBR 
optimized background regimen 
PK 
pharmacokinetics 
q2wk 
every 2 weeks 
q4wk 
every 4 weeks 
QOL 
quality of life 
RNA 
ribonucleic acid 
SAE 
serious adverse event 
SAF 
safety dataset for analysis 


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ABBREVIATION 
TERM 
SD 
standard deviation 
TEAE 
treatment-emergent adverse event 
TFDA 
Taiwan Food and Drug Administration 
US 
United States 
USP 
United States Pharmacopoeia 
WHODD 
WHO Drug Dictionary 


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1. Introduction 
 
1.1 
Background 
Antiretroviral medications for treatment of human immunodeficiency virus (HIV) have evolved 
tremendously over recent years. Efficacy and tolerability have improved as well as the convenience 
of treatment regimens. The percentage of patients on treatment who maintain viral suppression 
approaches 75%-80%.1,2 Unfortunately, some patients harbor strains of HIV that are resistant to 
currently available therapies. Patients with multi-drug resistant (MDR) HIV have limited or no 
treatment options. Department of Health and Human Services (HHS) HIV treatment guidelines 
encourage these patients to seek clinical trials and expanded access programs.3   
 
TaiMed Biologics is currently developing ibalizumab for treatment of HIV. Ibalizumab is a 
monoclonal antibody that binds to a conformational epitope on domain 2 of the extracellular 
portion of the CD4 receptor. Ibalizumab binding reduces HIV replication by inhibiting viral entry 
into CD4+ T-cells. With this novel mechanism of action, ibalizumab has no known cross-resistance 
with other antiretroviral medications. Ibalizumab in combination with other antiretroviral 
medications has demonstrated safety and durable antiviral activity in clinical trials in HIV-1-infected, 
treatment-experienced patients with MDR HIV. Ibalizumab has been awarded Orphan Drug and 
Breakthrough Drug designations by the US Food and Drug Administration (FDA). Still, the clinical 
trial and regulatory approval process can take several years to complete; some patients who are in 
urgent need of treatment cannot wait for ibalizumab to secure approval. An expanded access to 
clinical trial is needed to provide potentially life-saving access for patients with MDR HIV and 
limited or no available treatment options.  
 
 
1.2 
Clinical Studies 
Prior studies have been conducted in HIV-positive individuals using the IV formulation of 
ibalizumab, and are summarized here. In addition, a study of ibalizumab administered 
subcutaneously (TMB-108) to HIV-negative at-risk volunteers has been completed. Another study 
(TMB-121) exploring both subcutaneous and intramuscular administration routes in both HIV-
negative and HIV-positive participants is ongoing. 
 


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Results from the Phase 1a clinical trial (Hu5A8.01) demonstrated that IV administration of a single 
dose of ibalizumab to HIV-infected patients was associated with dose-dependent mean viral load 
reductions of approximately 1 log10 in those receiving doses of 10 mg/kg or greater. Mean viral load 
reductions persisted for 2-3 weeks. In a subsequent Phase 1b study (TNX-355.02), ibalizumab was 
given to HIV-infected patients as a single agent (monotherapy) or added to failing highly active 
antiretroviral therapy (HAART). Multiple doses of ibalizumab again demonstrated clinically 
significant viral load reductions (median reductions approximately 1 log10) with viral load nadirs at 1-
2 weeks. A 24-week, double-blind, placebo-controlled, randomized, three-arm Phase 2a study 
(TNX-355.03) evaluated the safety, efficacy, and pharmacokinetics (PK) activity of two ibalizumab 
dose regimens (10 mg/kg and 15 mg/kg) in combination with an optimized background regimen 
(OBR) versus placebo with an OBR in treatment-experienced patients. As in the Phase 1 program, 
the Phase 2a study clearly demonstrated the antiviral activity of ibalizumab. Viral load reductions in 
the treatment arms were statistically significantly different from placebo, with approximately 1 log10 
reductions seen in the ibalizumab-containing arms at 24 weeks (primary endpoint) and 48 weeks. 
Also at 48 weeks, increases in CD4+ T-cell counts of approximately +50 cells/µL were observed for 
both of the active treatment arms versus virtually no change from baseline for the placebo arm (+1 
cell/µL). 
 
All single-dose and multiple-dose administrations of ibalizumab were generally well tolerated with 
no serious adverse events (SAEs) related to study drug, no dose-limiting toxicities related to study 
drug, and no evidence of adverse effects on the CD4+ T-cells of treated patients. When compared to 
placebo (Phase 2a) the incidences, spectrum, and intensity of AEs were similar between the active 
treatment arms and the placebo arm. While a statistically significant difference in incidence was not 
observed between either of the active treatment arms and the placebo arm, rash (mostly mild to 
moderate severity) did occur more often in active treatment arms than in the placebo arm. This 
observation appears to be consistent with the known association of rash with administration of 
humanized monoclonal antibody (MAb) medications.4 The administration of ibalizumab was not 
associated with immunosuppression, as evidenced by the lack of any increase in infections or 
malignancies in the study population treated with ibalizumab. Intradermal skin tests performed on a 
subset of patients were also similar between active treatment arms and placebo. Anti-ibalizumab 
antibodies have been detected transiently and at low titers in a small number of patients (2.4%). The 
observation of anti-ibalizumab antibody activity was not associated with any AEs and appeared to 
have no impact on antiviral efficacy. The significance of anti-ibalizumab antibodies is not known. 
 


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A Phase 2b clinical trial in 113 HIV-infected patients was also completed. Heavily treatment-
experienced patients enrolled in this study received IV doses of 800 mg of ibalizumab every 2 weeks 
(q2wk) or 2,000 mg every 4 weeks (q4wk) in combination with an OBR. The key primary efficacy 
endpoint was the proportion of patients with HIV-1 ribonucleic acid (RNA) levels below the assay 
limit (<50 copies/mL) at Week 24. The percentages of patients with <50 copies/mL at Week 24 
were 44% and 28% for the 800 mg q2wk arm and the 2,000 mg q4wk arm respectively, in the most 
stringent intention-to-treat (ITT) missing equals failure (MEF) analysis. Other noteworthy efficacy 
endpoints included mean change from Baseline in HIV-1 RNA at Week 24 and mean change in 
CD4+ T-cell counts. The mean change from Baseline at Week 24 was -1.6 log10 for the 800 mg q2wk 
arm and -1.5 log10 for the 2,000 mg q4wk arm. The mean change from Baseline in CD4+ T-cells at 
Week 24 was +37 cells/μL for the 800 mg q2wk group and +40 cells/μL for the 2,000 mg q4wk 
group. These results are consistent with quantitative measures of immune system recovery in a 
treatment-experienced population over 24 weeks in studies of other drugs. There was no statistically 
significant difference between the 800 mg q2wk and 2,000 mg q4wk arms in viral load outcomes at 
24 weeks. 
 
Similar to previous studies, ibalizumab in combination with the OBR was well tolerated in the Phase 
2b investigation. The incidences, spectrum, and intensity of AEs were similar across the two 
treatment arms. A total of 15 SAEs were reported in 14 randomized patients, and all SAEs were 
assessed as not related to study drug. The most frequent non-laboratory AEs were rash (13%), 
diarrhea (12%), and headache (9%); most did not result in discontinuation. Other clinical treatment-
emergent adverse events (TEAEs) that were reported in ≥ 5% of patients were nausea, 
nasopharyngitis, upper respiratory tract infection, cough, oral candidiasis, vomiting, and fatigue. 
Only rash and headache were considered treatment-related TEAEs in ≥ 5% of patients on study. 
One treatment-related TEAE (moderate rash) resulted in study discontinuation. Based on the overall 
study results, the 800 mg q2wk dose and the 2,000 mg q4wk dose demonstrated safety and efficacy 
in this treatment-experienced HIV-positive patient population. 
 
A subcutaneous formulation of ibalizumab has been developed and an initial Phase 1 clinical trial 
(TMB-108) conducted. TMB-108 was a randomized, placebo-controlled, double-blind, multi-dose 
sequential escalating dose study. The dosing cohorts were 120 mg, 240 mg, and 480 mg each given 
weekly. Each subject received weekly doses of ibalizumab subcutaneously for 4 weeks. Subjects who 
withdrew prior to completion of dosing for non-safety-related reasons were replaced. 
 


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No SAEs and no discontinuations due to AEs were reported on the protocol. No Grade 4 AEs 
were reported. One Grade 3 AE, “headache,” was reported. This AE was treated with over-the-
counter medications and resolved within one day of onset. Headache was also the most frequently 
reported AE, with all other reports of headache being mild to moderate in intensity. In addition to 
headache, AEs reported in more than one patient were cough, sinus/nasal congestion, and pruritis. 
No injection site reactions were reported. Taken together, the reported results of completed clinical 
studies suggest that ibalizumab is safe and has potent activity against HIV in humans. 
 
The phase 3 registrational study (TMB-301) was a single arm, multicenter study, conducted in 40 
treatment-experienced HIV-infected patients with multi-drug resistant HIV-1. Patients were treated 
with antiretrovirals for at least 6 months and were failing or had recently failed (i.e., in the last 8 
weeks) therapy to determine baseline viral load with documented HIV viral load of >1,000 
copies/mL.   
 
During Days 0 through 6, “the control period”, patients were monitored on current failing 
background regimen (or no therapy, if the patient had failed and discontinued treatment within the 8 
weeks preceding Screening). During Days 7 through 13, "the essential monotherapy period", 
patients continued on current failing therapy and received one 2000 mg dose (loading dose) of 
ibalizumab on Day 7. Day 7 was Baseline for the treatment period (Day 7-Week 25). On Day 14, 
viral load was assessed for the primary end point, thereafter the background regimen was optimized 
to include at least one agent to which the patient’s virus was susceptible. Beginning at Day 21, 800 
mg of ibalizumab was administered every 2 weeks through Week 23, the “maintenance period”. 
Thirty-one patients completed the Week 25/ End of Study Visit. The primary effectiveness endpoint 
was the proportion of patients achieving a ≥0.5 log10 decrease in viral load from Day 0 to Day 7 
and from Day 7 to Day 14. 
 
At Baseline, median viral load and CD4+ T cell counts were 4.55 log10 copies/mL (35,350 
copies/mL) and 73 cells/mm3, respectively. Baseline Overall Susceptibility Scores (OSS) was were 
0, 1, 2, or ≥2, for X (X13%), XX (X35%), XXX (X45%), and 3% of patients,  for 0, 1, and ≥2, 
respectively.  
 
In the ITT population, a statistically significant difference was observed between the proportion of 
patients achieving a  0.5 log10 decrease in viral load from Day 0 to Day 7 (Control period; 2.5%; 
95% CI: 0.0006, 0.1316) and compared with the proportion achieving a  0.5 log10 decrease from 
Day 7 to Day 14 after receiving a 2000 mg loading dose of ibalizumab (82.5%; 95% CI: 0.6722, 


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0.9266; p<0.0001). Sixty Fifty five percent of patients achieved ≥1.0 log10 reduction in viral load 
after receiving the 2000 mg loading dose, during the essential monotherapy period (Day 7 to Day 
14), and 55%after receiving the 2000 mg loading dose. maintained a ≥1.0 log10 reduction in viral 
load after receiving the and 800 mg q wk dose at once weekly through Week 25, during the 
maintenance period. during the essential monotherapy period (Day 7 to Day 14). The mean change 
in viral load from Baseline to Day 14 was  a 1.07 log 10  reduction and to Week 25 was a 1.64 log 10 
reduction at Day 14 was a 1.07 log10 reduction. 
 
An increase in the mean number of CD4+ T-cells of 63 cell/μL was observed from Baseline to 
Week 25.  This increase in CD4+ T-cells is indicative of the therapeutic effect over 24 weeks. 
At Week 25 after treatment with the 800 mg a 2wk maintenance dose, the mean change in viral load 
from Day 7 was 1.6 log10 reduction with 55% and 48% of patients having a ≥1 log10 and ≥2 log10 
reduction, respectively. Viral load <50 and <200 HIV-1 RNA copies/mL was reached in 43% and 
50% of patients, respectively.  
 
The most common adverse reactions (all Grades) reported in at least 5% of subjects were diarrhea, 
dizziness, nausea, and rash.  Table 1 shows the frequency of adverse reactions occurring in 5% or 
more of subjects.  
 
Table 1. 
 Adverse Reactions (All Grades) Reported in ≥5% of Subjects 
Receiving ibalizumab and Optimized Background Regimen for 23 Weeks in Trial 
TMB-301 
                                                                      
 
 
 
 
                                                                      
 
 
*Includes pooled terms “rash”, “rash erythematous”, “rash generalized”, “rash macular”, “rash 
maculopapular”, and “rash papular” 
 
Most (90%) of the adverse reactions reported were mild or moderate in severity.  Two subjects 
experienced severe adverse reactions: one subject had a severe rash and one subject developed 
immune reconstitution inflammatory syndrome manifested as an exacerbation of progressive 
multifocal leukoencephalopathy.  
 
 
Percent of All TMB-301 Subjects  
(N=40) 
n (%) 
Diarrhea 
3 (8%) 
Dizziness 
3 (8%) 
Nausea 
2 (5%) 
Rash* 
2 (5%) 


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Laboratory Abnormalities 
Table 2. Selected Laboratory Abnormalities (≥Grade 3) in Trial TMB-301 
% Subjects 
N=40 
Bilirubin (≥ 2.6 x ULN) 
5% 
Direct Bilirubin (> ULN) 
3% 
Creatinine (>1.8x ULN or 1.5x baseline) 
10% 
Blood Glucose (> 250 mg/dL) 
3%  
Lipase (>3.0 x ULN) 
5% 
Uric Acid (>12 mg/dL)  
3% 
Hemoglobin (< 8.5 g/dL) 
3% 
Platelets (< 50,000/mm3) 
3% 
Leukocytes (< 1.5 109 cells/L) 
5% 
 
Neutrophils (<0.6 109 cells/L) 
5% 
 
As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody 
formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the 
observed incidence of antibody (including neutralizing antibody) positivity in an assay may be 
influenced by several factors including assay methodology, sample handling, timing of sample 
collection, concomitant medications, and underlying disease. For these reasons, comparison of the 
incidence of antibodies to ibalizumab in the studies described below with the incidence of antibodies 
in other studies or to other products may be misleading.  All subjects enrolled in clinical trial TMB-
301 and trial TMB-202 (a Phase 2b clinical trial that studied ibalizumab administered intravenously 
as 2,000 mg every 4 weeks or 800 mg every 2 weeks; the safety and effectiveness of this dosing 
regimen has not been established), were tested for the presence of anti-ibalizumab IgG antibodies 
throughout their participation. One sample tested positive with low titer anti-ibalizumab antibodies. 
No adverse reaction or reduced efficacy was attributed to the positive sample reported in this 
subject.  
 


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1.3 
Pharmacokinetic Profile 
IV administration of escalating single doses of ibalizumab (Protocol Hu5A8.01) demonstrated that 
serum concentrations of ibalizumab generally peaked at the end of the infusion period. Ibalizumab 
PKs were dose-dependent, as both systemic exposure and elimination half-life increased 
disproportionately with increasing dose. This indicated that the elimination of ibalizumab is capacity 
limited and saturable at higher doses. A similar conclusion was reached after a multiple-dose study 
of IV ibalizumab (Protocol TNX-355.02), which demonstrated that the steady state half-life 
following multiple doses of 10 and 25 mg/kg was 75 and 79 hours, respectively. The capacity-limited 
elimination is likely due to CD4 receptor turnover, given the short half-life for ibalizumab relative to 
endogenous IgG4 molecules. In the IV ibalizumab studies conducted to date, there was a correlation 
between ibalizumab trough serum concentrations of 0.3 µg/mL or higher and saturated binding of 
CD4 (receptor occupancy) on CD4+ T-cells, and between CD4 receptor occupancy and reductions 
in HIV viral load. Similar observations were made after subcutaneous administration of ibalizumab 
in HIV-negative volunteers, in which dose-dependent systemic exposure indicated saturable 
elimination with the same correlation between serum concentrations and CD4 receptor occupancy. 
A new study (TMB-121) of parenterally administered ibalizumab (subcutaneous and intramuscular) 
has been initiated to evaluate viral load responses in HIV-infected patients. 
 
 
 


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2. Study Objectives 
 
2.1 
Primary Objectives 
The primary objectives of this study are to: 
 
Cohort 1 
◼ 
Continue to provide ibalizumab to patients currently receiving ibalizumab treatment 
under Investigator-sponsored IND or TaiMed-sponsored protocols 
◼ 
Demonstrate the safety and tolerability of ibalizumab in HIV-positive patients with 
MDR HIV infection 
Cohort 2 
◼ 
Provide access to ibalizumab for qualifying MDR HIV-1-infected patients with limited 
treatment options 
◼ 
Demonstrate the safety and tolerability of ibalizumab in HIV-positive patients with 
MDR HIV infection 
 
2.2 
Secondary Objectives 
The secondary objectives of this study are to: 
 
◼ 
Demonstrate the antiviral activity of ibalizumab in HIV-positive patients with MDR 
HIV infection 
◼ 
Characterize HIV-1 sensitivity/susceptibility changes associated with protocol-defined 
virologic failure after ibalizumab administration in combination with the OBR 
◼ 
Determine the presence and significance of anti-ibalizumab antibodies associated with 
protocol-defined virologic failure after ibalizumab administration, if any 
(immunogenicity of ibalizumab) 


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3. Study Plan 
 
3.1 
Overall Design 
This Phase 3, multicenter, expanded access study will evaluate the safety and tolerability of 
ibalizumab in treatment-experienced patients infected with MDR HIV-1. Eligible patients will 
include (1) those currently receiving ibalizumab under a TaiMed-sponsored or Investigator-
sponsored IND protocol and (2) treatment-experienced patients with no history of ibalizumab 
treatment who are on a failing regimen, or who have failed and are off treatment.   
 
Patients will be enrolled in one of two Cohorts (Cohort 1 and Cohort 2): 
 
Cohort 1 (continuing treatment) 
◼ 
Patients will continue on an ibalizumab containing regimen at their current dosage in 
combination with a current OBR.   
Cohort 2 (initiating ibalizumab) 
◼ 
On Day 0/Baseline, patients will receive one 2,000 mg dose (loading dose) of 
ibalizumab. The OBR will be initiated on Day 0/Baseline and must include at least one 
agent to which the patient’s virus is susceptible.  
◼ 
Beginning at Day 14, an 800 mg of ibalizumab will be administered every 2 weeks 
through the remainder of the study. 
Virologic failure is defined as two consecutive measurements at Week 24 or later if less than a 0.5 
log10 decline from the Baseline viral load (see Section 9.4 for the definition of Baseline). 
 
Patients will be discontinued from the study at the patient’s request or if the patient becomes 
pregnant, at investigator request, for protocol violation, for virologic failure, for treatment-related 
serious or intolerable AE(s) (Division of AIDS [DAIDS] criteria, see Appendix B), or for toxicity 
(defined as two consecutive laboratory results, at least 14 days apart, with a CD4+ cell count below 
200 cells/mm3 that also represents a 50% reduction from the Baseline CD4+ cell count). 
 
 


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3.2 
Discussion of Trial Design 
This study is designed to assess the safety and tolerability of IV ibalizumab. In addition, all patients 
will receive a standard of care OBR consisting of antiretroviral medications selected by the Principal 
Investigator based upon the patient's treatment history and the results of viral resistance testing. The 
effectiveness of the treatment regimen will also be assessed (Cohort 2 only). Safety and tolerability 
will be evaluated by the occurrence of AEs and discontinuations. The primary evaluation of 
effectiveness will be at Day 7. Additional secondary evaluations will be conducted at Day 7 and 
other assessment time points. 
 
This is an open-label safety study to provide early access to IV ibalizumab for HIV-1-infected 
patients who have no or limited treatment options on commercially available antiretroviral therapy 
(ART) and who are ineligible for participation in any other TaiMed Biologics-sponsored trial of 
ibalizumab. The safety and tolerability of IV ibalizumab in combination with an OBR in MDR HIV-
1-infected patients with limited or no treatment options will be assessed. Eligible patients already 
approved for Investigator-sponsored ibalizumab INDs (Cohort 1) will remain on Investigator-
sponsored INDs until they can be transitioned to this protocol. Upon enrollment, patients will 
continue to receive treatment with the previously assigned regimen: either ibalizumab 800 mg IV 
every 2 weeks with an OBR, or ibalizumab 2,000 mg IV every 4 weeks with an OBR. Treatment will 
continue until treatment-limiting toxicity, virologic failure, loss to follow-up, withdrawal from the 
trial, pregnancy, discontinuation of ibalizumab development, or commercial availability of 
ibalizumab. 
 
Eligible patients participating in TaiMed Protocol TMB-301 (who will enroll in Cohort 1 of this 
study) will continue to receive treatment with ibalizumab 800 mg IV every 2 weeks with an OBR 
while enrolled in this study. Treatment will continue until treatment-limiting toxicity, virologic 
failure, loss to follow-up, withdrawal from the trial, pregnancy, discontinuation of ibalizumab 
development, or commercial availability of ibalizumab. 
 
Eligible patients who are not participating in an Investigator-sponsored or TaiMed-sponsored 
ibalizumab IND (Cohort 2 of this study) will undergo a Screening period of, at most, 6 weeks. 
Patients will start treatment with ibalizumab 2,000 mg IV (loading) on Day 0 and then 800 mg IV 
(maintenance) on Day 14 and every 2 weeks thereafter. All patients will also receive an OBR 
beginning at Day 0. Treatment will continue until treatment-limiting toxicity, virologic failure, loss to 


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follow-up, withdrawal from the trial, pregnancy, discontinuation of ibalizumab development, or 
commercial availability of ibalizumab. 
 
 
3.3 
Dose Selection 
Both dosages of IV ibalizumab (2,000 mg every 4 weeks and 800 mg every 2 weeks) were evaluated 
in the TMB-202 Phase 2b study. The results of that study indicated that higher serum concentrations 
and maximum receptor occupancy were achieved more rapidly with the 2,000 mg dose. Conversely, 
a higher percentage of patients on the 800 mg dose administered every 2 weeks achieved and 
maintained HIV RNA levels below 50 copies at Week 24 compared to patients on the 2,000 mg 
dose administered every 4 weeks. This observation may have been associated with the trend toward 
higher trough concentrations observed with the 800 mg dose. As the AE profile of both dosages 
was similar, the dosage regimen selected for Cohort 2 (patients initiating ibalizumab) in this study 
reflects the optimal PK features of each dose studied in TMB-202: A single 2,000 mg loading dose 
will be followed by 800 mg maintenance doses administered every 2 weeks. This dose regimen is 
designed to combine the maximal initial drug exposure of a 2,000 mg dosage with the more durable 
exposure of the 800 mg q2week dosage. Cohort 1 patients (continuing treatment) will continue on 
their current successful dosing regimens. 
 
 
3.4 
Schedule of Events 
The Schedule of Events is presented in Tables 3-1 and 3-2 for Cohort 1 patients receiving 
ibalizumab 800 mg every 2 weeks, in Tables 3-3 and 3-4 for Cohort 1 patients receiving ibalizumab 
2,000 mg every 4 weeks, and in Tables 3-5 and 3-6 for patients in Cohort 2. Throughout the study, 
patients are not required to fast before collection of blood samples for safety or effectiveness. 
However, patients should adhere to dietary recommendations as suggested for the components of 
their OBR or other concomitant medications. 
 
 


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Table 3-1. 
Schedule of Events: Cohort 1 – 800 mg every 2 weeks, Screening through Week 4 
 
Study Visit 
Screening/ 
Day 0 
Day 14 
Week 4 
Visit window (days) 
N/A 
±1 
±2 
ACTIVITIES TO BE COMPLETED BEFORE STUDY DRUG ADMINISTRATION 
 
 
 
Discuss the inclusion/exclusion criteria 
X 
 
 
Obtain a signed informed consent form  
X 
 
 
Record demographics, medical history (general and HIV), height 
X 
 
 
Record all prior ART exposure; record all other medications within the last 30 days 
X 
 
 
Assess adherence to the OBR 
 
 
X 
Record results of a complete physical examination 
X 
 
 
Record vital sign measurements 
X 
X 
X 
Record the patient’s weight 
X 
 
 
Record AEs 
X4 
X 
X 
Record concomitant medications 
 
X 
X 
BLOOD 1 AND/OR URINE SAMPLES TO BE COLLECTED BEFORE STUDY DRUG ADMINISTRATION 
 
 
 
Hepatitis serology, C-reactive protein 
X 
 
 
Hematology, serum chemistry, urinalysis (see Section 7.2.2) 
X 
 
 
Archive sample 
X 
 
 
Serum for pregnancy test for females of childbearing potential 2  
X 
 
 
Urine for pregnancy test for females of childbearing potential  
 
 
X 
HIV-1 RNA (viral load) 
X 
 
 
HIV-1 viral resistance sample 3  
X 
 
 
CD4+ T-cell count 5 
X 
 
 
Immunogenicity of ibalizumab (2 tubes x 3 mL each) 5 
X 
 
 
STUDY DRUG ADMINISTRATION AND AFTER 
 
 
 
Administer study medication 
X 
X 
X 
Record vital sign measurements and observe (15 min.) after infusion 
X 
X 
X 
Record AEs 
X 
X 
X 
 
 


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1 Patients need not fast before blood sampling. 
2 Serum FSH test to be conducted on postmenopausal females at Screening only. 
3 Viral resistance testing will include assessments of reverse transcriptase, protease, integrase, and envelope (entry) genes and chemokine coreceptor utilization; the samples will be 
collected and stored, and testing will only be performed for patients who experience virologic failure while on the study. 
4 Only record AEs that are related to study procedures before administration of the first dose. 
5 Samples to be drawn within 1 hour before the start of the infusion (if infusion is scheduled for that visit). 
 
Abbreviations: AE = adverse event; ART = antiretroviral therapy; CD4+ = helper T-cell; FSH = follicle-stimulating hormone; HIV = human immunodeficiency virus; OBR = optimized background 
regimen 
 
 


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Table 3-2. 
Schedule of Events: Cohort 1 – 800 mg every 2 weeks, Week 6 through end of study 
Week 
Study Visit 
6 
8 
10 
12 
14 
16 
18 
20 
22 
24 
26 
Visit window (days) 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
ACTIVITIES TO BE COMPLETED BEFORE STUDY DRUG 
ADMINISTRATION 
 
 
 
 
 
 
 
 
 
 
 
Record results of a complete physical examination 
 
 
 
 
 
 
 
 
 
X 
 
Record results of an abbreviated physical examination 1 
 
 
 
X 
 
 
 
 
 
 
 
Record the patient’s weight  
 
 
 
X 
 
 
 
 
 
X 
 
Record vital sign measurements 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Record AEs and concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assess adherence to the OBR 
 
X 
 
X 
 
 
 
 
 
X 
 
BLOOD 2 AND/OR URINE SAMPLES TO BE COLLECTED BEFORE 
STUDY DRUG ADMINISTRATION 
 
 
 
 
 
 
 
 
 
 
 
Hepatitis serology, C-reactive protein 
 
 
 
 
 
 
 
 
 
X 
 
Hematology, serum chemistry, urinalysis (see Section 7.2.2) 
 
 
 
X 
 
 
 
 
 
X 
 
Archive sample 
 
 
 
X 
 
 
 
 
 
X 
 
Serum for pregnancy test for females of childbearing potential  
 
 
 
 
 
 
 
 
 
X 
 
Urine for pregnancy test for females of childbearing potential  
 
X 
 
X 
 
X 
 
X 
 
 
 
HIV-1 RNA (viral load) 
 
 
 
X 
 
 
 
 
 
X 
 
HIV-1 viral resistance sample 3 
 
 
 
X 
 
 
 
 
 
X 
 
CD4+ T-cell count 4 
 
 
 
X 
 
 
 
 
 
X 
 
Immunogenicity of ibalizumab (2 tubes x 3 mL each) 4 
 
 
 
 
 
 
 
 
 
X 
 
STUDY DRUG ADMINISTRATION AND AFTER 
 
 
 
 
 
 
 
 
 
 
 
Administer study medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Record vital sign measurements and AEs and observe (15 min.) after infusion 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 


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23 
 
 
 
Table 3-2. 
Schedule of Events: Cohort 1 – 800 mg every 2 weeks, Week 6 through end of study (Continued) 
Week 
Study Visit 
28 
30 
32 
34 
36 
38 
40 
42 
44 
46 
48 
50 
52 
Visit window (days) 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
ACTIVITIES TO BE COMPLETED BEFORE STUDY DRUG 
ADMINISTRATION 
 
 
 
 
 
 
 
 
 
 
 
 
 
Record results of a complete physical examination 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Record results of an abbreviated physical examination 1 
 
 
 
 
X 
 
 
 
 
 
 
 
 
Record the patient’s weight  
 
 
 
 
X 
 
 
 
 
 
X 
 
 
Record vital sign measurements 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Records AEs and concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assess adherence to the OBR 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
BLOOD 2 AND/OR URINE SAMPLES TO BE COLLECTED 
BEFORE STUDY DRUG ADMINISTRATION 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hepatitis serology, C-reactive protein 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Hematology, serum chemistry, urinalysis (see Section 7.2.2) 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
Archive sample 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
Serum for pregnancy test for females of childbearing potential 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Urine for pregnancy test for females of childbearing potential  
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
HIV-1 RNA (viral load) 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
HIV-1 viral resistance sample 3 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
CD4+ T-cell count 4 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
Immunogenicity of ibalizumab (2 tubes x 3 mL each) 4 
 
 
 
 
 
 
 
 
 
 
X 
 
 
STUDY DRUG ADMINISTRATION AND AFTER 
 
 
 
 
 
 
 
 
 
 
 
 
 
Administer study medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Record vital sign measurements and AEs and observe (15 min.) 
after infusion 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 


TAIMED BIOLOGICS, INC. 
CONFIDENTIAL 
PROTOCOL: TMB-311 
DATE: 11 DECEMBER 2017 
 
 
Use or disclosure of data contained on this page is subject  
to the restriction on the title page of this proposal or quotation. 
24 
 
 
 
Table 3-2. 
Schedule of Events: Cohort 1 – 800 mg every 2 weeks, Week 6 through end of study (Continued) 
Week 
Study Visit 
54 
56 
58 
60 
62 
64 
66 
68 
70 
72 
74 
76 
78 
Visit window (days) 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
ACTIVITIES TO BE COMPLETED BEFORE STUDY DRUG 
ADMINISTRATION 
 
 
 
 
 
 
 
 
 
 
 
 
 
Record results of a complete physical examination 
 
 
 
 
 
 
 
 
 
X 
 
 
 
Record results of an abbreviated physical examination 1 
 
 
 
X 
 
 
 
 
 
 
 
 
 
Record the patient’s weight  
 
 
 
X 
 
 
 
 
 
X 
 
 
 
Record vital sign measurements 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Records AEs and concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assess adherence to the OBR 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
BLOOD 2 AND/OR URINE SAMPLES TO BE COLLECTED 
BEFORE STUDY DRUG ADMINISTRATION 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hepatitis serology, C-reactive protein 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology, serum chemistry, urinalysis (see Section 7.2.2) 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
Archive sample 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
Serum for pregnancy test for females of childbearing potential 
 
 
 
 
 
 
 
 
 
X 
 
 
 
Urine for pregnancy test for females of childbearing potential  
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
 
HIV-1 RNA (viral load) 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
HIV-1 viral resistance sample 3 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
CD4+ T-cell count 4 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
Immunogenicity of ibalizumab (2 tubes x 3 mL each) 4  
 
 
 
 
 
 
 
 
 
X 
 
 
 
STUDY DRUG ADMINISTRATION AND AFTER 
 
 
 
 
 
 
 
 
 
 
 
 
 
Administer study medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Record vital sign measurements and AEs and observe (15 min.) 
after infusion 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 


TAIMED BIOLOGICS, INC. 
CONFIDENTIAL 
PROTOCOL: TMB-311 
DATE: 11 DECEMBER 2017 
 
 
Use or disclosure of data contained on this page is subject  
to the restriction on the title page of this proposal or quotation. 
25 
 
 
 
Table 3-2. 
Schedule of Events: Cohort 1 – 800 mg every 2 weeks, Week 6 through end of study (Continued) 
Week 
Study Visit 
80 
82 
84 
86 
88 
90 
92 
94 
96 
98 
100 
102 
104 
Visit window (days) 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
ACTIVITIES TO BE COMPLETED BEFORE STUDY DRUG 
ADMINISTRATION 
 
 
 
 
 
 
 
 
 
 
 
 
 
Record results of a complete physical examination 
 
 
 
 
 
 
 
 
X 
 
 
 
 
Record results of an abbreviated physical examination 1 
 
 
 
 
 
 
 
 
 
 
 
 
 
Record the patient’s weight  
 
 
 
 
 
 
 
 
X 
 
 
 
 
Record vital sign measurements 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Records AEs and concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assess adherence to the OBR 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
BLOOD 2 AND/OR URINE SAMPLES TO BE COLLECTED 
BEFORE STUDY DRUG ADMINISTRATION 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hepatitis serology, C-reactive protein 
 
 
 
 
 
 
 
 
X 
 
 
 
 
Hematology, serum chemistry, urinalysis (see Section 7.2.2) 
 
 
 
 
 
 
 
 
X 
 
 
 
 
Archive sample 
 
 
 
 
 
 
 
 
X 
 
 
 
 
Serum for pregnancy test for females of childbearing potential 
 
 
 
 
 
 
 
 
X 
 
 
 
 
Urine for pregnancy test for females of childbearing potential  
X 
 
X 
 
X 
 
X 
 
 
 
X 
 
X 
HIV-1 RNA (viral load) 
 
 
 
 
 
 
 
 
X 
 
 
 
 
HIV-1 viral resistance sample 3 
 
 
 
 
 
 
 
 
X 
 
 
 
 
CD4+ T-cell count 4 
 
 
 
 
 
 
 
 
X 
 
 
 
 
Immunogenicity of ibalizumab (2 tubes x 3 mL each) 4 
 
 
 
 
 
 
 
 
X 
 
 
 
 
STUDY DRUG ADMINISTRATION AND AFTER 
 
 
 
 
 
 
 
 
 
 
 
 
 
Administer study medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Record vital sign measurements and AEs and observe (15 min.) 
after infusion 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 


TAIMED BIOLOGICS, INC. 
CONFIDENTIAL 
PROTOCOL: TMB-311 
DATE: 11 DECEMBER 2017 
 
 
Use or disclosure of data contained on this page is subject  
to the restriction on the title page of this proposal or quotation. 
26 
 
 
 
Table 3-2. 
Schedule of Events: Cohort 1 – 800 mg every 2 weeks, Week 6 through end of study (Continued) 
Week 
Study Visit 
106 
108 
110 
112 
114 
116 
118 
120 
122 
124 
126 
128 
130 
Visit window (days) 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
ACTIVITIES TO BE COMPLETED BEFORE STUDY DRUG 
ADMINISTRATION 
 
 
 
 
 
 
 
 
 
 
 
 
 
Record results of a complete physical examination 
 
 
 
 
 
 
 
X 
 
 
 
 
 
Record results of an abbreviated physical examination 1 
 
 
 
 
 
 
 
 
 
 
 
 
 
Record the patient’s weight  
 
 
 
 
 
 
 
X 
 
 
 
 
 
Record vital sign measurements 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Records AEs and concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assess adherence to the OBR 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
BLOOD 2 AND/OR URINE SAMPLES TO BE COLLECTED 
BEFORE STUDY DRUG ADMINISTRATION 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hepatitis serology, C-reactive protein 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology, serum chemistry, urinalysis (see Section 7.2.2) 
 
 
 
 
 
 
 
X 
 
 
 
 
 
Archive sample 
 
 
 
 
 
 
 
X 
 
 
 
 
 
Serum for pregnancy test for females of childbearing potential 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine for pregnancy test for females of childbearing potential  
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
HIV-1 RNA (viral load) 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
HIV-1 viral resistance sample 3 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
CD4+ T-cell count 4 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
Immunogenicity of ibalizumab (2 tubes x 3 mL each) 4 
 
 
 
 
 
 
 
X 
 
 
 
 
 
STUDY DRUG ADMINISTRATION AND AFTER 
 
 
 
 
 
 
 
 
 
 
 
 
 
Administer study medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Record vital sign measurements and AEs and observe (15 min.) 
after infusion 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 


TAIMED BIOLOGICS, INC. 
CONFIDENTIAL 
PROTOCOL: TMB-311 
DATE: 11 DECEMBER 2017 
 
 
Use or disclosure of data contained on this page is subject  
to the restriction on the title page of this proposal or quotation. 
27 
 
 
 
Table 3-2. 
Schedule of Events: Cohort 1 – 800 mg every 2 weeks, Week 6 through end of study (Continued) 
Week 
Study Visit 
132 
134 
136 
138 
140 
142 
144/ 
EOS 
150/ 
Follow up 
Early 
Withdrawal5 
Visit window (days) 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
 
ACTIVITIES TO BE COMPLETED BEFORE STUDY DRUG 
ADMINISTRATION 
 
 
 
 
 
 
 
 
 
Record results of a complete physical examination 
 
 
 
 
 
 
X 
X 
X 
Record results of an abbreviated physical examination 1 
 
 
 
 
 
 
 
 
 
Record the patient’s weight  
 
 
 
 
 
 
X 
X 
X 
Record vital sign measurements 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Records AEs and concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assess adherence to the OBR 
X 
 
 
 
 
 
X 
X 
X 
BLOOD 2 AND/OR URINE SAMPLES TO BE COLLECTED 
BEFORE STUDY DRUG ADMINISTRATION 
 
 
 
 
 
 
 
 
 
Hepatitis serology, C-reactive protein 
 
 
 
 
 
 
 
X 
X 
Hematology, serum chemistry, urinalysis (see Section 7.2.2) 
 
 
 
 
 
 
 
X 
X 
Archive sample 
 
 
 
 
 
 
X 
X 
X 
Serum for pregnancy test for females of childbearing potential 
 
 
 
 
 
 
 
 
X 
Urine for pregnancy test for females of childbearing potential  
X 
 
X 
 
X 
 
X 
X 
 
HIV-1 RNA (viral load) 
X 
 
 
 
 
 
X 
X 
X 
HIV-1 viral resistance sample 3 
X 
 
 
 
 
 
X 
X 
X 
CD4+ T-cell count 4 
X 
 
 
 
 
 
X 
X 
X 
Immunogenicity of ibalizumab (2 tubes x 3 mL each) 4 
 
 
 
 
 
 
X 
X 
X 
STUDY DRUG ADMINISTRATION AND AFTER 
 
 
 
 
 
 
 
 
 
Administer study medication 
X 
X 
X 
X 
X 
X 
X 
 
 
Record vital sign measurements and AEs and observe (15 min.) 
after infusion 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 


TAIMED BIOLOGICS, INC. 
CONFIDENTIAL 
PROTOCOL: TMB-311 
DATE: 11 DECEMBER 2017 
 
 
Use or disclosure of data contained on this page is subject  
to the restriction on the title page of this proposal or quotation. 
28 
 
 
 
1 Abbreviated physical examination will include an examination of lymph nodes, respiratory and cardiovascular systems, abdomen, extremities, and nervous system. 
2 Patients need not fast before blood sampling. 
3 Viral resistance testing will include assessments of reverse transcriptase, protease, integrase, and envelope (entry) genes and chemokine coreceptor utilization; the samples will be 
collected and stored, and testing will only be performed for patients who experience virologic failure while on the study. 
4 Samples to be drawn within 1 hour before the start of the infusion (if infusion is scheduled for that visit). 
5 Patients who withdraw or are withdrawn at any time prior to the Week 150 visit should have Early Withdrawal procedures performed. 
 
Abbreviations: AE = adverse event; ART = antiretroviral therapy; CD4+ = helper T-cell; EOS = end of study; FSH = follicle-stimulating hormone; HIV = human immunodeficiency virus; OBR = 
optimized background regimen 
 
 


TAIMED BIOLOGICS, INC. 
CONFIDENTIAL 
PROTOCOL: TMB-311 
DATE: 11 DECEMBER 2017 
 
 
Use or disclosure of data contained on this page is subject  
to the restriction on the title page of this proposal or quotation. 
29 
 
 
 
Table 3-3. 
Schedule of Events: Cohort 1 – 2,000 mg every 4 weeks, Screening through Week 8 
 
Study Visit 
Screening/ 
Day 0 
Week 4 
Week 8 
Visit window (days) 
N/A 
±2 
±2 
ACTIVITIES TO BE COMPLETED BEFORE STUDY DRUG ADMINISTRATION 
 
 
 
Discuss the inclusion/exclusion criteria 
X 
 
 
Obtain a signed informed consent form  
X 
 
 
Record demographics, medical history (general and HIV), height 
X 
 
 
Record all prior ART exposure; record all other medications within the last 30 days 
X 
 
 
Assess adherence to the OBR 
 
X 
X 
Record results of a complete physical examination 
X 
 
 
Record vital sign measurements 
X 
X 
X 
Record the patient’s weight 
X 
 
 
Record AEs 
X 
X 
X 
Record concomitant medications 
 
X 
X 
BLOOD 1 AND/OR URINE SAMPLES TO BE COLLECTED BEFORE STUDY DRUG 
ADMINISTRATION 
 
 
 
Hepatitis serology, C-reactive protein 
X 
 
 
Hematology, serum chemistry, urinalysis (see Section 7.2.2) 
X 
 
 
Archive sample 
X 
 
 
Serum for pregnancy test for females of childbearing potential 2  
X 
 
 
Urine for pregnancy test for females of childbearing potential  
 
X 
X 
HIV-1 RNA (viral load) 
X 
 
 
HIV-1 viral resistance sample 3  
X 
 
 
CD4+ T-cell count 4 
X 
 
 
Immunogenicity of ibalizumab (2 tubes x 3 mL each) 4 
X 
 
 
STUDY DRUG ADMINISTRATION AND AFTER 
 
 
 
Administer study medication 
X 
X 
X 
Record vital sign measurements and observe (15 min.) after infusion 
X 
X 
X 
Record AEs 
X 
X 
X 
 
 


TAIMED BIOLOGICS, INC. 
CONFIDENTIAL 
PROTOCOL: TMB-311 
DATE: 11 DECEMBER 2017 
 
 
Use or disclosure of data contained on this page is subject  
to the restriction on the title page of this proposal or quotation. 
30 
 
 
 
1 Patients need not fast before blood sampling. 
2 Serum FSH test to be conducted on postmenopausal females at Screening only. 
3 Viral resistance testing will include assessments of reverse transcriptase, protease, integrase, and envelope (entry) genes and chemokine coreceptor utilization; the samples will be 
collected and stored, and testing will only be performed for patients who experience virologic failure while on the study. 
4 Samples to be drawn within 1 hour before the start of the infusion (if infusion is scheduled for that visit). 
 
Abbreviations: AE = adverse event; ART = antiretroviral therapy; CD4+ = helper T-cell; FSH = follicle-stimulating hormone; HIV = human immunodeficiency virus; OBR = optimized background 
regimen 
 
 


TAIMED BIOLOGICS, INC. 
CONFIDENTIAL 
PROTOCOL: TMB-311 
DATE: 11 DECEMBER 2017 
 
 
Use or disclosure of data contained on this page is subject  
to the restriction on the title page of this proposal or quotation. 
31 
 
 
 
Table 3-4. 
Schedule of Events: Cohort 1 – 2,000 mg every 4 weeks, Week 12 through end of study 
Week 
Study Visit 
12 
16 
20 
24 
28 
32 
36 
40 
44 
48 
52 
56 
Visit window (days) 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
ACTIVITIES TO BE COMPLETED BEFORE STUDY DRUG 
ADMINISTRATION 
 
 
 
 
 
 
 
 
 
 
 
 
Record results of a complete physical examination 
 
 
 
X 
 
 
 
 
 
X 
 
 
Record results of an abbreviated physical examination 1 
X 
 
 
 
 
 
X 
 
 
 
 
 
Record the patient’s weight  
X 
 
 
X 
 
 
X 
 
 
X 
 
 
Record vital sign measurements 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Record AEs and concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assess adherence to the OBR 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
BLOOD 2 AND/OR URINE SAMPLES TO BE COLLECTED BEFORE 
STUDY DRUG ADMINISTRATION 
 
 
 
 
 
 
 
 
 
 
 
 
Hepatitis serology, C-reactive protein 
 
 
 
X 
 
 
 
 
 
X 
 
 
Hematology, serum chemistry, urinalysis (see Section 7.2.2) 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
Archive sample 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
Serum for pregnancy test for females of childbearing potential  
 
 
 
X 
 
 
 
 
 
X 
 
 
Urine for pregnancy test for females of childbearing potential  
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
HIV-1 RNA (viral load) 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
HIV-1 viral resistance sample 3 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
CD4+ T-cell count 4 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
Immunogenicity of ibalizumab (2 tubes x 3 mL each) 4 
 
 
 
X 
 
 
 
 
 
X 
 
 
STUDY DRUG ADMINISTRATION AND AFTER 
 
 
 
 
 
 
 
 
 
 
 
 
Administer study medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Record vital sign measurements and AEs and observe (15 min.) after infusion 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 


TAIMED BIOLOGICS, INC. 
CONFIDENTIAL 
PROTOCOL: TMB-311 
DATE: 11 DECEMBER 2017 
 
 
Use or disclosure of data contained on this page is subject  
to the restriction on the title page of this proposal or quotation. 
32 
 
 
 
Table 3-4. 
Schedule of Events: Cohort 1 – 2,000 mg every 4 weeks, Week 12 through end of study (Continued) 
Week 
Study Visit 
60 
64 
68 
72 
76 
80 
84 
88 
92 
96 
100 
104 
Visit window (days) 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
ACTIVITIES TO BE COMPLETED BEFORE STUDY DRUG 
ADMINISTRATION 
 
 
 
 
 
 
 
 
 
 
 
 
Record results of a complete physical examination 
 
 
 
X 
 
 
 
 
 
X 
 
 
Record results of an abbreviated physical examination 1 
X 
 
 
 
 
 
 
 
 
 
 
 
Record the patient’s weight  
X 
 
 
X 
 
 
 
 
 
X 
 
 
Record vital sign measurements 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Record AEs and concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assess adherence to the OBR 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
BLOOD 2 AND/OR URINE SAMPLES TO BE COLLECTED BEFORE 
STUDY DRUG ADMINISTRATION 
 
 
 
 
 
 
 
 
 
 
 
 
Hepatitis serology, C-reactive protein 
 
 
 
X 
 
 
 
 
 
X 
 
 
Hematology, serum chemistry, urinalysis (see Section 7.2.2) 
X 
 
 
X 
 
 
 
 
 
X 
 
 
Archive sample 
X 
 
 
X 
 
 
 
 
 
X 
 
 
Serum for pregnancy test for females of childbearing potential  
 
 
 
X 
 
 
 
 
 
X 
 
 
Urine for pregnancy test for females of childbearing potential  
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
HIV-1 RNA (viral load) 
X 
 
 
X 
 
 
 
 
 
X 
 
 
HIV-1 viral resistance sample 3 
X 
 
 
X 
 
 
 
 
 
X 
 
 
CD4+ T-cell count 4 
X 
 
 
X 
 
 
 
 
 
X 
 
 
Immunogenicity of ibalizumab (2 tubes x 3 mL each) 4 
 
 
 
X 
 
 
 
 
 
X 
 
 
STUDY DRUG ADMINISTRATION AND AFTER 
 
 
 
 
 
 
 
 
 
 
 
 
Administer study medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Record vital sign measurements and AEs and observe (15 min.) after infusion 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 


TAIMED BIOLOGICS, INC. 
CONFIDENTIAL 
PROTOCOL: TMB-311 
DATE: 11 DECEMBER 2017 
 
 
Use or disclosure of data contained on this page is subject  
to the restriction on the title page of this proposal or quotation. 
33 
 
 
 
Table 3-4. 
Schedule of Events: Cohort 1 – 2,000 mg every 4 weeks, Week 12 through end of study (Continued) 
Week 
Study Visit 
108 112 116 120 124 128 132 136 140 
144 
EOS 
150 
Follow up 
Early 
Withdrawal5 
Visit window (days) 
±2 ±2 ±2 ±2 ±2 ±2 ±2 ±2 ±2 
±2 
±2 
 
ACTIVITIES TO BE COMPLETED BEFORE STUDY DRUG 
ADMINISTRATION 
 
 
 
 
 
 
 
 
 
 
 
 
Record results of a complete physical examination 
 
 
 
X 
 
 
 
 
 
X 
X 
X 
Record results of an abbreviated physical examination 1 
 
 
 
 
 
 
 
 
 
 
 
 
Record the patient’s weight  
 
 
 
X 
 
 
 
 
 
X 
X 
X 
Record vital sign measurements 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Record AEs and concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assess adherence to the OBR 
X 
 
 
X 
 
 
X 
 
 
X 
X 
X 
BLOOD 2 AND/OR URINE SAMPLES TO BE COLLECTED BEFORE 
STUDY DRUG ADMINISTRATION 
 
 
 
 
 
 
 
 
 
 
 
 
Hepatitis serology, C-reactive protein 
 
 
 
 
 
 
 
 
 
 
X 
X 
Hematology, serum chemistry, urinalysis (see Section 7.2.2) 
 
 
 
X 
 
 
 
 
 
 
X 
X 
Archive sample 
 
 
 
X 
 
 
 
 
 
X 
X 
X 
Serum for pregnancy test for females of childbearing potential  
 
 
 
 
 
 
 
 
 
 
 
X 
Urine for pregnancy test for females of childbearing potential  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
HIV-1 RNA (viral load) 
X 
 
 
X 
 
 
X 
 
 
X 
X 
X 
HIV-1 viral resistance sample 3 
X 
 
 
X 
 
 
X 
 
 
X 
X 
X 
CD4+ T-cell count 4 
X 
 
 
X 
 
 
X 
 
 
X 
X 
X 
Immunogenicity of ibalizumab (2 tubes x 3 mL each) 4 
 
 
 
X 
 
 
 
 
 
X 
X 
X 
STUDY DRUG ADMINISTRATION AND AFTER 
 
 
 
 
 
 
 
 
 
 
 
 
Administer study medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Record vital sign measurements and AEs and observe (15 min.) after infusion 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 


TAIMED BIOLOGICS, INC. 
CONFIDENTIAL 
PROTOCOL: TMB-311 
DATE: 11 DECEMBER 2017 
 
 
Use or disclosure of data contained on this page is subject  
to the restriction on the title page of this proposal or quotation. 
34 
 
 
 
1 Abbreviated physical examination will include an examination of lymph nodes, respiratory and cardiovascular systems, abdomen, extremities, and nervous system. 
2 Patients need not fast before blood sampling. 
3 Viral resistance testing will include assessments of reverse transcriptase, protease, integrase, and envelope (entry) genes and chemokine coreceptor utilization; the samples will be 
collected and stored, and testing will only be performed for patients who experience virologic failure while on the study. 
4  Samples to be drawn within 1 hour before the start of the infusion (if infusion is scheduled for that visit). 
5 Patients who withdraw or are withdrawn at any time prior to the Week 150 visit should have Early Withdrawal procedures performed. 
 
Abbreviations: AE = adverse event; ART = antiretroviral therapy; CD4+ = helper T-cell; EOS = end of study; FSH = follicle-stimulating hormone; HIV = human immunodeficiency virus; OBR = 
optimized background regimen 
 
 


TAIMED BIOLOGICS, INC. 
CONFIDENTIAL 
PROTOCOL: TMB-311 
DATE: 11 DECEMBER 2017 
 
 
Use or disclosure of data contained on this page is subject  
to the restriction on the title page of this proposal or quotation. 
35 
 
 
 
Table 3-5. 
Schedule of Events: Cohort 2, Screening through Day 14 
 
Screening 
Study Visit 
Weeks -6 to -1 
Day 0 
Baseline 
Day 7 
Day 14 
Visit window (days) 
N/A 
N/A 
±1 
±1 
ACTIVITIES TO BE COMPLETED BEFORE STUDY DRUG ADMINISTRATION 
 
 
 
 
Discuss the inclusion/exclusion criteria 
X 
 
 
 
Obtain a signed informed consent form  
X 
 
 
 
Record demographics, medical history (general and HIV), height 
X 
 
 
 
Record all prior ART exposure or changes to ART; record all other medications within the last 30 
days1 
X 
X 
 
 
Obtain documentation of HIV-1 infection 2 
X 
 
 
 
Obtain documentation of viral resistance, if available (within 6 months of Screening); select OBR 
X 
 
 
 
Initiate the selected OBR 
 
X 
 
 
Assess adherence to the OBR 
 
 
X 
 
Record results of a complete physical examination 
X 
X 
 
 
Record results of an abbreviated physical examination 3 
 
 
X 
 
Record vital sign measurements 
X 
X 
X 
X 
Record the patient’s weight 
X 
X 
 
 
Record AEs 
X4 
X 4  
X 
X 
Record concomitant medications 
 
 
X 
X 
BLOOD 5 AND/OR URINE SAMPLES TO BE COLLECTED BEFORE STUDY DRUG 
ADMINISTRATION 
 
 
 
 
Hepatitis serology, C-reactive protein 
X 
 
 
 
Hematology, serum chemistry, urinalysis (see Section 7.2.2) 
X 
X 
X 
 
Archive sample 
 
X 
X 
 
Serum for pregnancy test for females of childbearing potential 6  
X 
 
 
 
Urine for pregnancy test for females of childbearing potential  
 
X 
 
 
HIV-1 RNA (viral load) 
X 
X 
X 
X 
HIV-1 antibody level, if written documentation not provided 
X 
 
 
 
HIV-1 viral resistance sample 7  
X 
X 
X 
X 
CD4+ T-cell count 8 
X 
X 
X 
X 
Immunogenicity of ibalizumab (2 tubes x 3 mL each) 8 
 
X 
 
 
 
 


TAIMED BIOLOGICS, INC. 
CONFIDENTIAL 
PROTOCOL: TMB-311 
DATE: 11 DECEMBER 2017 
 
 
Use or disclosure of data contained on this page is subject  
to the restriction on the title page of this proposal or quotation. 
36 
 
 
 
Table 3-5. 
Schedule of Events: Cohort 2, Screening through Day 14 (Continued) 
 
Screening 
Study Visit 
Weeks -6 to -1 
Day 0 
Baseline 
Day 7 
Day 14 
STUDY DRUG ADMINISTRATION AND AFTER 
 
 
 
 
Administer study medication 9 
 
X 
 
X 
Record vital sign measurements after infusion10 
 
X 
 
X 
Record AEs 
 
X 
 
X 
 
1 All prior ART will be recorded at Screening; Day 0 visit will only record changes to ART. 
2 An HIV antibody test will be completed at Screening if official, signed, written documentation is unavailable. 
3 Abbreviated physical examination includes examination of lymph nodes, respiratory and cardiovascular systems, abdomen, extremities, and nervous system. 
4 Only record AEs that are related to study procedures before administration of the first dose. 
5 Patients need not fast before blood sampling. 
6 Serum FSH test to be conducted on postmenopausal females at Screening only. 
7 Viral resistance testing will include assessments of reverse transcriptase, protease, integrase, and envelope (entry) genes and chemokine coreceptor utilization; the samples will be 
collected and stored, and testing will only be performed for patients who experience virologic failure while on the study. 
8 Samples to be drawn within 1 hour before the start of the infusion (if infusion is scheduled for that visit). 
9  All patients in Cohort 2 must be observed for 1 hour after the completion of study drug administration. If the patient does not experience an AE(s) related to the infusion (local or systemic) 
through and including the second infusion on Day 14, then the observation time can be reduced to 15 minutes thereafter. 
10 Record vital signs after infusion (if infusion is completed at that visit). 
Abbreviations: AE = adverse event; ART = antiretroviral therapy; CD4+ = helper T-cell; FSH = follicle-stimulating hormone; HIV = human immunodeficiency virus; OBR = optimized background 
regimen 
 
 
 


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Table 3-6. 
Schedule of Events: Cohort 2, Week 4 through end of study 
Week 
Study Visit 
4 
6 
8 
10 
12 
14 
16 
18 
20 
22 
24 
26 
Visit window (days) 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
ACTIVITIES TO BE COMPLETED BEFORE STUDY DRUG 
ADMINISTRATION 
 
 
 
 
 
 
 
 
 
 
 
 
Record results of a complete physical examination 
X 
 
 
 
 
 
 
 
 
 
X 
 
Record results of an abbreviated physical examination 1 
 
 
 
 
X 
 
 
 
X 
 
 
 
Record the patient’s weight  
X 
 
 
 
X 
 
 
 
X 
 
X 
 
Record vital sign measurements 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Record AEs and concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assess adherence to the OBR 
X 
 
X  
 
X 
 
 
 
X 
 
X 
 
BLOOD 2 AND/OR URINE SAMPLES TO BE COLLECTED BEFORE 
STUDY DRUG ADMINISTRATION 
 
 
 
 
 
 
 
 
 
 
 
 
Hepatitis serology, C-reactive protein 
 
 
 
 
 
 
 
 
 
 
X 
 
Hematology, serum chemistry, urinalysis (see Section 7.2.2) 
 
 
 
 
X 
 
 
 
 
 
X 
 
Archive sample 
 
 
 
 
X 
 
 
 
 
 
X 
 
Serum for pregnancy test for females of childbearing potential  
 
 
 
 
 
 
 
 
 
 
X 
 
Urine for pregnancy test for females of childbearing potential  
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
HIV-1 RNA (viral load) 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
HIV-1 viral resistance sample 3 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
CD4+ T-cell count 4 
X 
X   s 
X 
 
X 
 
X 
 
X 
 
X 
 
Immunogenicity of ibalizumab (2 tubes x 3 mL each) 4 
 
 
 
 
 
 
 
 
 
 
X 
 
STUDY DRUG ADMINISTRATION AND AFTER 
 
 
 
 
 
 
 
 
 
 
 
 
Administer study medication 5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Record vital sign measurements and AEs after infusion 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 


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Table 3-6. 
Schedule of Events: Cohort 2, Week 4 through end of study (Continued) 
Week 
Study Visit 
28 
30 
32 
34 
36 
38 
40 
42 
44 
46 
48 
50 
52 
Visit window (days) 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
ACTIVITIES TO BE COMPLETED BEFORE STUDY DRUG 
ADMINISTRATION 
 
 
 
 
 
 
 
 
 
 
 
 
 
Record results of a complete physical examination 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Record results of an abbreviated physical examination 1 
 
 
X 
 
 
 
X 
 
 
 
 
 
 
Record the patient’s weight  
 
 
X 
 
X 
 
X 
 
 
 
X 
 
 
Record vital sign measurements 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Records AEs and concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assess adherence to the OBR 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
BLOOD 2 AND/OR URINE SAMPLES TO BE COLLECTED 
BEFORE STUDY DRUG ADMINISTRATION 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hepatitis serology, C-reactive protein 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Hematology, serum chemistry, urinalysis (see Section 7.2.2) 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
Archive sample 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
Serum for pregnancy test for females of childbearing potential 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Urine for pregnancy test for females of childbearing potential  
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
HIV-1 RNA (viral load) 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
HIV-1 viral resistance sample 3 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
CD4+ T-cell count 4 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
Immunogenicity of ibalizumab (2 tubes x 3 mL each) 4  
 
 
 
 
 
 
 
 
 
 
X 
 
 
STUDY DRUG ADMINISTRATION AND AFTER 
 
 
 
 
 
 
 
 
 
 
 
 
 
Administer study medication 5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Record vital sign measurements and AEs after infusion 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 


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Table 3-6. 
Schedule of Events: Cohort 2, Week 4 through end of study (Continued) 
Week 
Study Visit 
54 
56 
58 
60 
62 
64 
66 
68 
70 
72 
74 
76 
78 
Visit window (days) 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
ACTIVITIES TO BE COMPLETED BEFORE STUDY DRUG 
ADMINISTRATION 
 
 
 
 
 
 
 
 
 
 
 
 
 
Record results of a complete physical examination 
 
 
 
 
 
 
 
 
 
X 
 
 
 
Record results of an abbreviated physical examination 1 
 
 
 
X 
 
 
 
 
 
 
 
 
 
Record the patient’s weight  
 
 
 
X 
 
 
 
 
 
X 
 
 
 
Record vital sign measurements 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Records AEs and concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assess adherence to the OBR 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
BLOOD 2 AND/OR URINE SAMPLES TO BE COLLECTED 
BEFORE STUDY DRUG ADMINISTRATION 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hepatitis serology, C-reactive protein 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology, serum chemistry, urinalysis (see Section 7.2.2) 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
Archive sample 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
Serum for pregnancy test for females of childbearing potential 
 
 
 
 
 
 
 
 
 
X 
 
 
 
Urine for pregnancy test for females of childbearing potential  
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
 
HIV-1 RNA (viral load) 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
HIV-1 viral resistance sample 3 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
CD4+ T-cell count 4 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
Immunogenicity of ibalizumab (2 tubes x 3 mL each) 4  
 
 
 
 
 
 
 
 
 
X 
 
 
 
STUDY DRUG ADMINISTRATION AND AFTER 
 
 
 
 
 
 
 
 
 
 
 
 
 
Administer study medication 5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Record vital sign measurements and AEs after infusion 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 


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Table 3-6. 
Schedule of Events: Cohort 2, Week 4 through end of study (Continued) 
Week 
Study Visit 
80 
82 
84 
86 
88 
90 
92 
94 
96 
98 
100 
102 
104 
Visit window (days) 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
ACTIVITIES TO BE COMPLETED BEFORE STUDY DRUG 
ADMINISTRATION 
 
 
 
 
 
 
 
 
 
 
 
 
 
Record results of a complete physical examination 
 
 
 
 
 
 
 
 
X 
 
 
 
 
Record results of an abbreviated physical examination 1 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Record the patient’s weight  
 
 
X 
 
 
 
 
 
X 
 
 
 
 
Record vital sign measurements 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Records AEs and concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assess adherence to the OBR 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
BLOOD 2 AND/OR URINE SAMPLES TO BE COLLECTED 
BEFORE STUDY DRUG ADMINISTRATION 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hepatitis serology, C-reactive protein 
 
 
 
 
 
 
 
 
X 
 
 
 
 
Hematology, serum chemistry, urinalysis (see Section 7.2.2) 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
Archive sample 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
Serum for pregnancy test for females of childbearing potential 
 
 
 
 
 
 
 
 
X 
 
 
 
 
Urine for pregnancy test for females of childbearing potential  
X 
 
X 
 
X 
 
X 
 
 
 
X 
 
X 
HIV-1 RNA (viral load) 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
HIV-1 viral resistance sample 3 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
CD4+ T-cell count 4 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
Immunogenicity of ibalizumab (2 tubes x 3 mL each) 4  
 
 
 
 
 
 
 
 
X 
 
 
 
 
STUDY DRUG ADMINISTRATION AND AFTER 
 
 
 
 
 
 
 
 
 
 
 
 
 
Administer study medication 5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Record vital sign measurements and AEs after infusion 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 


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Table 3-6. 
Schedule of Events: Cohort 2, Week 4 through end of study (Continued) 
Week 
Study Visit 
106 
108 
110 
112 
114 
116 
118 
120 
122 
124 
126 
128 
130 
Visit window (days) 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
ACTIVITIES TO BE COMPLETED BEFORE STUDY DRUG 
ADMINISTRATION 
 
 
 
 
 
 
 
 
 
 
 
 
 
Record results of a complete physical examination 
 
 
 
 
 
 
 
X 
 
 
 
 
 
Record results of an abbreviated physical examination 1 
 
 
 
 
 
 
 
 
 
 
 
 
 
Record the patient’s weight  
 
 
 
 
 
 
 
X 
 
 
 
 
 
Record vital sign measurements 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Records AEs and concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assess adherence to the OBR 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
BLOOD 2 AND/OR URINE SAMPLES TO BE COLLECTED 
BEFORE STUDY DRUG ADMINISTRATION 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hepatitis serology, C-reactive protein 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology, serum chemistry, urinalysis (see Section 7.2.2) 
 
 
 
 
 
 
 
X 
 
 
 
 
 
Archive sample 
 
 
 
 
 
 
 
X 
 
 
 
 
 
Serum for pregnancy test for females of childbearing potential 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine for pregnancy test for females of childbearing potential  
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
HIV-1 RNA (viral load) 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
HIV-1 viral resistance sample 3 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
CD4+ T-cell count 4 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
Immunogenicity of ibalizumab (2 tubes x 3 mL each) 4  
 
 
 
 
 
 
 
X 
 
 
 
 
 
STUDY DRUG ADMINISTRATION AND AFTER 
 
 
 
 
 
 
 
 
 
 
 
 
 
Administer study medication 5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Record vital sign measurements and AEs after infusion 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 


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Table 3-6. 
Schedule of Events: Cohort 2, Week 4 through end of study (Continued) 
Week 
Study Visit 
132 
134 
136 
138 
140 
142 
144/ 
EOS 
150/ 
Follow up 
Early 
Withdrawal6 
Visit window (days) 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
 
ACTIVITIES TO BE COMPLETED BEFORE STUDY DRUG 
ADMINISTRATION 
 
 
 
 
 
 
 
 
 
Record results of a complete physical examination 
 
 
 
 
 
 
X 
X 
X 
Record results of an abbreviated physical examination 1 
 
 
 
 
 
 
 
 
 
Record the patient’s weight  
 
 
 
 
 
 
X 
X 
X 
Record vital sign measurements 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Records AEs and concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assess adherence to the OBR 
X 
 
 
 
 
 
X 
X 
X 
BLOOD 2 AND/OR URINE SAMPLES TO BE COLLECTED 
BEFORE STUDY DRUG ADMINISTRATION 
 
 
 
 
 
 
 
 
 
Hepatitis serology, C-reactive protein 
 
 
 
 
 
 
 
X 
X 
Hematology, serum chemistry, urinalysis (see Section 7.2.2) 
 
 
 
 
 
 
 
X 
X 
Archive sample 
 
 
 
 
 
 
X 
X 
X 
Serum for pregnancy test for females of childbearing potential 
 
 
 
 
 
 
 
 
X 
Urine for pregnancy test for females of childbearing potential  
X 
 
X 
 
X 
 
X 
X 
 
HIV-1 RNA (viral load) 
X 
 
 
 
 
 
X 
X 
X 
HIV-1 viral resistance sample 3 
X 
 
 
 
 
 
X 
X 
X 
CD4+ T-cell count 4 
X 
 
 
 
 
 
X 
X 
X 
Immunogenicity of ibalizumab (2 tubes x 3 mL each) 4  
 
 
 
 
 
 
X 
X 
X 
STUDY DRUG ADMINISTRATION AND AFTER 
 
 
 
 
 
 
 
 
 
Administer study medication 5 
X 
X 
X 
X 
X 
X 
X 
 
 
Record vital sign measurements and AEs after infusion 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 


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1 Abbreviated physical examination includes examination of lymph nodes, respiratory and cardiovascular systems, abdomen, extremities, and nervous system. 
2  Patients need not fast before blood sampling. 
3  Viral resistance testing will include assessments of reverse transcriptase, protease, integrase, and envelope (entry) genes and chemokine coreceptor utilization; the samples will be 
collected and stored, and testing will only be performed for patients who experience virologic failure while on the study. 
4 Samples are to be drawn within 1 hour before the start of the infusion (if infusion is scheduled for that visit). 
5  All patients in Cohort 2 must be observed for 1 hour after the completion of study drug administration. If the patient does not experience an AE(s) related to the infusion (local or systemic) 
through and including the second infusion on Day 14, then the observation time can be reduced to 15 minutes thereafter. 
6 Patients who withdraw or are withdrawn at any time prior to the Week 102 visit should have Early Withdrawal procedures performed. 
Abbreviations: AE = adverse event; ART = antiretroviral therapy; CD4+ = helper T-cell; EOS = end of study; FSH = follicle-stimulating hormone; HIV = human immunodeficiency virus; OBR = 
optimized background regimen 
 


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3.5 
Effectiveness Assessments 
The primary effectiveness variable is the proportion of patients achieving a ≥0.5 log10 decrease from 
Baseline in viral load at Day 7 (assessed for Cohort 2 only). 
 
Secondary effectiveness variables will be the following: 
 
◼ 
Proportion of patients with HIV-1 RNA levels <50 copies/mL and <400 copies/mL at 
assessment time points (assessed for Cohort 2 only) 
◼ 
Mean change from Baseline in viral load at Day 7 and all assessment time points 
(assessed for Cohort 2 only) 
◼ 
Proportion of patients achieving a ≥0.5 log10 and ≥1.0 log10 decrease from Baseline in 
viral load at all assessment time points (assessed for Cohort 2 only) 
◼ 
HIV-1 sensitivity/susceptibility changes associated with virologic failure after 
administration of ibalizumab 
 
3.6 
Safety Assessments 
Safety assessments will include the results of the following measurements throughout the study: 
 
◼ 
Physical examinations 
◼ 
Vital sign measurements 
◼ 
Clinical laboratory parameters (hematology, serum chemistry, and urinalysis) 
◼ 
Monitoring of AEs and concomitant medications 
◼ 
Incidence of Class C events as defined by the Centers for Disease Control and 
Prevention (CDC) Classification System for HIV Infection (Appendix A) 
◼ 
Anti-ibalizumab antibody levels (immunogenicity of ibalizumab) 
 


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4. Study Treatments 
 
4.1 
Study Drug Dosage and Administration 
There are two different ibalizumab IV drug product vial configurations available for use in this 
study:  
 
Current Drug Lots In Use 
(1) vials with a 1.33 mL injection volume and 200 mg ibalizumab per vial (Lots 201509019 and 
201505012).  
 
Patients receiving ibalizumab in study TMB-301, who will enroll into Cohort 1 of this study, and 
patients initiating ibalizumab in Cohort 2 will receive only vials with a 1.33 mL injection volume and 
200 mg ibalizumab per vial.  
 
Previous Drug Lot that is Depleted 
(2) vials with a 1.2 mL injection volume and 180 mg ibalizumab per vial (Lot 201403001.  This 
information is provided only in the event that Cohort 1 sites, with patients who were previously 
under Investigator sponsored IND protocols, may still have this lot in their inventory). 
 
All ibalizumab drug product to be used in this study will be at a concentration of 150 mg/mL. 
 
 
 
 
4.1.1 
Cohort 1 
Patients in Cohort 1 will continue receiving ibalizumab via IV infusion at the currently assigned 
dosage: either 800 mg q2wk or 2,000 mg q4wk.  
 
 
(Lots 201509019 and 201505012) 
For patients enrolling into this study from study TMB-301, study drug will be provided in open-
labeled cartons of 10 vials at 1.33 mL/200 mg each. For the 800 mg q2wk doses, 4 vials are to be 


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used. Using a sterile syringe, 1.33 mL is withdrawn from each of the vials to be used and injected 
into a 250 mL infusion bag of normal saline. Administration of the prepared infusion should begin 
no more than 6 hours after the time of preparation. 
 
(Lot 201403001) 
Until the supply of drug product currently allocated for use in Cohort 1 patients enrolling from 
Investigator-sponsored INDs is exhausted, study drugs for these patients will continue to be 
provided in open-labeled cartons containing 10 vials at 1.2 mL/180 mg each.  
• For the 2,000 mg q4wk doses (adjusted to 2,010 mg for this vial configuration), 13.4 mL 
total volume of ibalizumab drug product is required for each administration.  
• For the 800 mg q2wk doses (adjusted to 810 mg for this vial configuration), 5.4 mL total 
volume of ibalizumab drug product is required for each administration.  
Using a sterile syringe, the required content is withdrawn from each of the vials to be used and 
injected into a 250 mL infusion bag of normal saline. Administration of the prepared infusion 
should begin no more than 6 hours after the time of preparation. 
 
When the 1.2 mL, 180 mg/vial drug product is exhausted, patients enrolled in Cohort 1 from 
Investigator-sponsored INDs will be switched to the 1.33 mL, 200 mg/vial drug product. Study 
drug will then be provided in open-labeled cartons of 10 vials at 1.33 mL/200 mg each.  
• For the 2,000 mg q4wk doses, all 10 vials in a carton are to be used.  
• For the 800 mg q2wk doses, 4 vials are to be used.  
Using a sterile syringe, 1.33 mL is withdrawn from each of the vials to be used and injected into a 
250 mL infusion bag of normal saline. Administration of the prepared infusion should begin no 
more than 6 hours after the time of preparation. 
 
4.1.2 
Cohort 2 
(Lots 201509019 and 201505012) 
Study drug will be administered via IV infusion at a dose of 2,000 mg on one occasion (Day 
0/Baseline), followed 2 weeks later (Day 14) by doses of 800 mg administered once every 2 weeks 
through the remainder of the study. 
 
Study drug will be provided in open-labeled cartons of 10 vials each.  
• For the 2,000 mg doses, all 10 vials in a carton are to be used.  
• For the 800 mg doses, four vials are to be used.  


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Using a sterile syringe, 1.33 mL is withdrawn from each of the vials to be used and injected into a 
250 mL infusion bag of normal saline. Administration of the prepared infusion should begin no 
more than 6 hours after the time of preparation. 
 
 
4.1.3 
Administration 
The infusion should be administered in the cephalic vein of the patient’s right or left arm. If this 
vein is not accessible, an appropriate vein located elsewhere can be used. For patients initiating 
ibalizumab in Cohort 2, the duration of the infusion should be no less than 30 minutes during the 
first two study drug administrations. If no infusion-associated AEs have occurred after two 
administrations, the duration of the infusion can be decreased to no less than 15 minutes.  
 
The start and stop times of each infusion will be recorded in an Electronic Data Capture (EDC) 
system, along with the site of administration. The date of use and the patient’s study identification 
(ID) number and initials will be recorded. 
 
All Cohort 2 patients must be observed for 1 hour after completion of study drug administration for 
at least the first two administrations (Day 0/Baseline and Day 14). If the patient does not experience 
an AE(s) related to the infusion (local or systemic) during the first two infusions, then the post-
infusion observation time can be reduced to 15 minutes thereafter. 
 
In addition to the study drug, all patients will receive an OBR, which is a standard-of-care regimen 
selected by the investigator based upon treatment history and the results of recent viral resistance 
testing. For patients enrolling into Cohort 2, previous resistance testing done within 6 months prior 
to Screening must demonstrate that the patient’s viral isolate is sensitive/susceptible to a minimum 
of one of the agents selected for the OBR. As part of the OBR, the patient must be willing and able 
to take at least one of the agents to which their virus is sensitive/susceptible. 
 
 
4.2 
Prohibited Medications and Restrictions 
Use of and changes in concomitant medications will be recorded in the patient’s source documents 
and the EDC system. All prescription drugs, herbal products, vitamins, minerals, and over-the-
counter medications are to be recorded. 


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Any concomitant medication, with the exception of those listed in Section 4.4.2 for Cohort 2 
patients, may be given at the discretion of the investigator. However, the investigator has the 
responsibility of ensuring that details regarding the concomitant medication are recorded for the 
patient in the EDC system. Complete information is expected for any medication prescribed during 
the trial. 
 
The prescribing information for all concomitant medications should be reviewed carefully. The 
guidance provided in the respective contraindications, warnings, and precautions section for any 
medication must be followed to prevent any potentially serious or life-threatening drug interactions. 
 
For patients enrolled into Cohort 2 only, the following medications are not to be administered 
concomitantly: 
 
◼ 
Therapeutic HIV vaccines from Screening until study participation ends 
◼ 
Any vaccines during the 7 days before Day 0/Baseline through Day 14 of the study 
◼ 
All investigational drugs from 30 days before Day 0/Baseline and throughout the study 
(except investigational antiretroviral medications as a component of the OBR) 
In addition, radiation therapy is not allowed for patients in Cohort 2 from 28 days before first 
administration of study drug to the last administration of study drug. Patients receiving radiation 
therapy are not allowed to enter Cohort 2 of the study; however, if a patient in Cohort 2 develops a 
condition that requires radiation but does not disqualify them from study participation for any other 
reason, then this event would need to be discussed with the medical monitor. 
 
First-dose, generalized, self-limiting skin rash has been described with therapeutic MAbs.5,6 Re-
challenge in such an event is at the discretion of the investigator. While there is no recommendation 
for premedication with diphenhydramine, acetaminophen, or corticosteroids, these medications have 
been used prior to the administration of other MAbs.7 Any patient who experiences anaphylactoid 
symptoms that are considered to be related to the study drug (possibly, probably, definitely) must 
have study drug discontinued and be withdrawn from the study immediately. Severe post-infusion 
reaction management typically includes corticosteroids, oxygen, and IV fluids, based on the severity 
and symptoms.7 Refer to Appendix C for further information on the management of suspected 
anaphylactoid reactions. Study drug should only be administered in a setting that allows for rapid 


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access to emergency cardiopulmonary support services in the event of a life-threatening infusion- 
related AE (e.g., anaphylaxis). 
 
 
4.3 
Measurement of Patient Adherence 
Patient adherence will require the availability of the patient at the study site to receive the dose and 
the patient’s willingness/ability to receive the entire dose. The receipt of the entire dose is assured, 
as each dose is given as an IV infusion by a trained professional from the clinical site and the event 
is recorded. Adherence to the OBR will also be recorded. 
 
 
4.4 
Missed Doses of Study Drug 
4.4.1 
Cohort 1 
Patients should receive study drug per the Schedule of Events (Section 3.4). A missed dose is 
defined as any dose of study drug that is not administered within the study visit window. Patients 
who miss doses of study medication for two consecutive dosing intervals (i.e., >28 days without a 
study drug infusion) of 800 mg dosage or one and one-half dosing intervals (i.e., >42 days without a 
study drug infusion) of the 2,000 mg dose may be withdrawn from the study.  
 
Missed Doses. If a dose is missed, the missed dose should be administered at the first opportunity. 
If an 800 mg dose is missed and cannot be administered at least 3 days before the next scheduled 
dose, it should be skipped. If a 2,000 mg dose is missed and cannot be administered at least 5 days 
before the next scheduled dose, it should be skipped.  
 
End of study (EOS) procedures should be performed as soon as possible after the patient qualifies 
for withdrawal due to missed doses. Patients who are withdrawn from the study for missed doses 
may not be permitted to participate in other ibalizumab protocols. 
 
 


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4.4.2 
Cohort 2 
Patients should receive study drug per the Schedule of Events (Section 3.4). A missed dose is 
defined as any dose of study drug that is not administered within the study visit window. Patients 
who miss doses of study medication for two consecutive dosing intervals (i.e., >28 days without a 
study drug infusion) or miss greater than two doses cumulatively will be withdrawn from the study. 
EOS procedures should be performed as soon as possible after the patient qualifies for withdrawal 
due to missed doses. Patients who are withdrawn from the study for missed doses may not be 
permitted to participate in other ibalizumab protocols. 
 
Missed Initial (Loading) Dose. If the initial 2,000 mg dose (loading dose) of study drug is 
administered outside the treatment window, the dose should be administered at the first available 
opportunity and the timing of subsequent doses should be adjusted to coincide with the actual 
administration time of the first dose. 
 
Missed Maintenance Dose (3-7 days). If a dose of 800 mg (maintenance dose) of study drug is 
missed by going beyond the scheduled dosing day by 3-7 days, a loading dose of 2,000 mg (reload) 
should be administered at the next available opportunity. The reload dose would substitute for the 
maintenance dose that was missed. All other visit procedures would not change other than the dose 
amount administered (i.e., 2,000 mg reload dose substituted for 800 mg maintenance dose). The 
scheduling of subsequent visits will not be adjusted. 
 
Example: If a patient is scheduled to receive study drug on Day 49 (Week 7) but cannot come in 
until Day 55, the patient should receive a 2,000 mg loading dose (reload) on Day 55. The subsequent 
dose should be 800 mg and scheduled for Day 63 (Week 9) (±2 day window). The patient should 
continue on the original visit schedule. 
 
Missed Maintenance Dose (>7 days and <14 days). If a dose of 800 mg (maintenance dose) of 
study drug is missed by going beyond the scheduled dosing day by more than 7 days but less than 14 
days, the patient should receive a 2,000 mg dose (reload) at the next available opportunity. The 
missed dose should be recorded as a missed dose/missed visit. A 2,000 mg reload dose administered 
between >7 days and <14 days beyond the scheduled dosing date will not substitute for the missed 
dose. The 2,000 mg reload dose will substitute for the next scheduled 800 mg maintenance dose. 
Study procedures for the visit subsequent to the missed dose/missed visit should be performed 
along with the administration of the 2,000 mg reload dose. The dosing schedule should be adjusted 


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such that the following 800 mg maintenance dose should be scheduled 2 weeks after the reload dose 
was administered. NOTE: Week 102/EOS procedures should be performed without regard to dose 
window whenever the visit occurs. 
 
Example: If a patient is scheduled to receive study drug on Day 49 (Week 7) but cannot come in 
until Day 58, the patient should receive a 2,000 mg loading dose (reload) on Day 58. Study 
procedures for Day 49 (Week 7) are recorded as missed. Study procedures for Day 63 (Week 9) are 
performed along with the administration of the 2,000 mg reload dose. The dose following the reload 
dose should be 800mg and scheduled for Day 72 (±2 day window). The visit schedule would be 
adjusted to 800 mg every 2 weeks from the day the drug was actually administered. 
 
No adjustments to dosage or dosing schedules are required for a missed dose that occurs before the 
dosing window. However, any dose administered before the dosing window is also considered a 
missed dose. 
 
 
4.5 
Study Drug Description 
The Sponsor or designee will provide the Research Pharmacists at the sites with vials containing 
study drug (active ibalizumab) manufactured under current Good Manufacturing Practices (cGMP). 
Ibalizumab is provided as a parenteral formulation in a 2 mL, clear-glass vial. The drug product 
contains ibalizumab at a concentration of 150 mg/mL, histidine United States Pharmacopoeia 
(USP), sucrose, sodium chloride, polysorbate 80, and water for injection USP at pH 6.0. Each vial 
contains either at least 1.2 mL of fluid delivering a total of 180 mg study drug per vial (Lot 
201403001) or at least 1.33 mL of fluid delivering a total of 200 mg study drug per vial (Lots 
201509019 and 201505012). Labeling will clearly identify the configuration of vials in each carton 
and of each individual vial. 
 
 
4.6 
Study Drug Packaging, Storage, and Disposal 
Study drug is provided as a single-use parenteral formulation in a 2 mL, clear-glass vial containing 
either at least 1.2 mL (Lot 204103001) or at least 1.33 mL (Lots 201509019 and 201505012) of drug 
product. The stability of the ibalizumab drug product at 2ºC to 8ºC is evaluated in ongoing studies. 
Study drug will be shipped under refrigerated conditions with a temperature-monitoring device. 


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Ibalizumab vials should be stored refrigerated at 2°C to 8°C (but NOT FROZEN) and protected 
from light. Investigator sites must store the investigational product in a secure location and maintain 
a temperature log of the storage conditions. 
 
The temperature must be continuously monitored with a continuous-monitoring temperature 
device. Temperature logs must be available for review at each site-monitoring visit. Temperature 
excursions outside the required limits should be reported promptly to the Sponsor, and the affected 
study drug should not be administered to any study patients until further instruction. The Sponsor 
or designee will investigate temperature excursions and adjudicate the disposition of any affected 
study drug. 
 
Any spent vials or remaining contents of used vials should be destroyed according to the site’s 
procedures for spent vial destruction and disposal, but only after complete drug accountability 
records have been reviewed and accepted during routine monitoring and after written permission 
has been given for spent vial destruction. The destruction should be recorded. 
 
 
4.7 
Study Drug Accountability 
The investigator will maintain accurate records of receipt of the entire supply of the study drug, 
including when, how much of, and conditions under which the study drug is received, dispensed, 
and destroyed by site personnel. In addition, the administration of study drug to each patient should 
be documented to the vial level for each infusion (i.e., lot number of every vial for that infusion, 
time of infusion bag preparation, time of administration, and documentation of full infusion 
received). Reasons for departure from the expected dispensing regimen must also be recorded. Drug 
accountability will be reviewed and documented at each study visit. Reconciliation and accountability 
of study drug will be done throughout the study during the monitoring visits. After the completion 
of the study, the Sponsor or designee may authorize the site to dispose of unused supplies of the 
investigational drug, provided this alternative disposition does not expose humans to risks from the 
drug. The Sponsor or designee shall maintain written records of all drug dispositions, which will 
include the name of the investigator; the date, quantity, batch, or code of each such shipment; and 
method of disposal. 
 
 


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5. Patient Enrollment 
 
It is anticipated that approximately 50 patients will be enrolled at approximately 50 sites in North 
America and Taiwan; however, the numbers of participating patients and sites will not be limited 
and may exceed 50. Patients will be enrolled only if they meet all of the inclusion criteria and none 
of the exclusion criteria. 
 
 
5.1 
Inclusion Criteria 
Patients may be enrolled in Cohort 1 if they meet both of the following criteria: 
1. Are currently receiving ibalizumab via other TaiMed-sponsored or Investigator-
sponsored IND protocol 
2. Are capable of understanding and have voluntarily signed the informed consent 
document 
Patients may be enrolled in Cohort 2 if they meet all of the following criteria: 
1. Are 18 years of age or older 
2. Are capable of understanding and have voluntarily signed the informed consent 
document 
3. Have documented HIV-1 infection by official, signed, written history (e.g., laboratory 
report); otherwise, an HIV-antibody test will be performed 
4. Are able and willing to comply with all protocol requirements and procedures 
5. Have a viral load >1,000 copies/mL and documented resistance to at least one 
antiretroviral medication from each of three classes of antiretroviral medications as 
measured by previous resistance testing (resistance testing is not provided by the study 
for qualification purposes) 
6. Have a history of at least 6 months on antiretroviral treatment 
7. Are receiving a failing antiretroviral regimen OR have failed and are off therapy  
8. Have viral sensitivity/susceptibility to at least one antiretroviral agent other than 
ibalizumab, as determined by previous resistance test performed within 6 months prior 
to Screening and be willing and able to be treated with at least one agent to which the 


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patient’s viral isolate is fully sensitive/susceptible according to the Screening resistance 
tests as a component of the OBR 
9. If sexually active, are willing to use an effective method of contraception during the 
study and for 30 days after the last administration of the study drug 
 
5.2 
Exclusion Criteria 
There are no Exclusion Criteria for patients meeting the Inclusion Criteria for Cohort 1. 
 
For Cohort 2, patients having or meeting any of the following conditions or characteristics will be 
excluded from the study: 
1. Eligible for participation in other TaiMed Biologics-sponsored clinical trials of ibalizumab 
2. Any significant diseases (other than HIV-1 infection) or clinically significant findings, 
including psychiatric and behavioral problems, determined from Screening, medical history, 
and/or physical examination that, in the investigator’s opinion, would preclude the patient 
from participating in this study 
3. Any significant acute illness within 1 week before the first administration of investigational 
medication on this study 
4. Any active infection secondary to HIV requiring acute therapy; however, patients who 
require maintenance therapy (i.e., secondary prophylaxis for opportunistic infections) will be 
eligible for the study 
5. Any immunomodulating therapy (including interferon), systemic steroids, or systemic 
chemotherapy within 4 weeks before Day 0 
6. Any prior exposure to ibalizumab (formerly TNX-355 and Hu5A8) 
7. Any vaccination within 7 days before Day 0 
8. Any female patient who is pregnant, intends to become pregnant, or is currently 
breastfeeding 
9. Any current alcohol or illicit drug use that, in the investigator’s opinion, will interfere with 
the patient’s ability to comply with the study schedule and protocol evaluations 
10. Any previous clinically significant allergy or hypersensitivity to any excipient in the 
ibalizumab formulation 


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11. Any radiation therapy during the 28 days before first administration of investigational 
medication on this study 
12. Any clinically significant Grade 3 or 4 laboratory abnormality according to the DAIDS 
grading scale, except for the following asymptomatic Grade 3 events: 
– 
triglyceride elevation 
– 
total cholesterol elevation 
 
 
 


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5.3 
Patient Withdrawal and Discontinuation 
5.3.1 
Reasons for Withdrawal 
A patient may be withdrawn from the study if the patient: 
 
◼ 
Withdraws consent to participate or requests an early discontinuation at any time during 
the study 
◼ 
Is in violation of the protocol 
◼ 
Becomes pregnant during the study (see Section 8.7 for a description of procedures to 
be followed in case of pregnancy) 
◼ 
Experiences virologic failure 
◼ 
Experiences a treatment-related serious or intolerable AE(s) (according to DAIDS 
criteria, see Appendix B) 
◼ 
Experiences toxicity, defined as two consecutive laboratory results, at least 14 days 
apart, with a CD4+ cell count below 200 cells/mm3 that also represents a 50% reduction 
from the baseline CD4+ cell count 
The study treatment should be discontinued for all Grade 3 or 4 treatment-related abnormalities, as 
defined in Appendix B. Treatment-emergent Grade 3 or Grade 4 lab abnormalities should be 
retested within 72 hours. Any patient with a Grade 3 or Grade 4 lab abnormality that resolves before 
the next scheduled dose may have the study drug reinstituted. If a patient develops a persistent 
Grade 3 or Grade 4 treatment-emergent laboratory abnormality, excluding triglycerides and 
cholesterol, that does not resolve prior to the next scheduled study drug administration, study drug 
may be discontinued. 
 
A patient experiencing one or more treatment-emergent SAEs will receive treatment and follow-up 
evaluations by the Principal Investigator, or they will be referred to another appropriate physician 
for treatment and follow-up. Withdrawal from the study will be at the discretion of the Principal 
Investigator/Sponsor. 
 
The investigator will also withdraw a patient if the Sponsor or local regulatory agency (e.g., FDA) 
terminates the study. Upon occurrence of an SAE, the Principal Investigator will notify the Sponsor 
or designee of these events via the SAE hotline. If a patient is discontinued because of an AE, the 


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event will be followed until satisfactory resolution or until the Principal Investigator deems the event 
to be chronic or the patient to be stable. 
 
 
5.3.2 
Handling Withdrawals and Discontinuations 
Patients are free to withdraw from the study at any time upon request. Patient participation in the 
trial may be stopped at any time at the discretion of the investigator or at the request of the Sponsor 
or designee. At the time of withdrawal or discontinuation, the investigator will assess the best 
options for treatment and discuss these options with the patient. 
 
When a patient withdraws or is discontinued from the study, the reason(s) for withdrawal or 
discontinuation will be recorded by the investigator. Whenever possible, all patients who withdraw, 
or are discontinued from the study prematurely, will undergo all Early Withdrawal procedures as 
described in the Schedule of Events in Section 3.4. Patients who fail to return for final assessments 
will be contacted by the site personnel in an attempt to have the patients comply with the protocol. 
A minimum of two documented phone calls should be made over the course of at least 2 weeks. If 
the site personnel receive no response, they should send a certified letter requesting that the patient 
contact the site regarding their status in the study. If the patient does not respond at this point, the 
date the certified letter was mailed will be considered the date of study withdrawal. 
 
In the event of a patient death during the study, the date of death (as listed on the death certificate) 
will be used for the date of study discontinuation. 
 
It is vital to obtain follow-up data on any patient withdrawn because of an AE or SAE. In such 
cases, the patient will be followed to satisfactory resolution or until the Principal Investigator deems 
the event to be chronic or the patient to be stable. In any case, every effort must be made to 
undertake protocol-specified safety follow-up procedures. 
 
 
5.3.3 
Sponsor or Regulatory Agency Termination of Study 
Although the Sponsor intends to complete the study, the right is reserved to discontinue the study at 
any time for clinical or administrative reasons, upon commercial availability of ibalizumab, or if 


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required by the local regulatory authority (e.g., FDA). If the Sponsor discontinues the study, the 
FDA will be notified promptly. 
 
 
6. Study Visits 
 
6.1 
Cohort 1: 800 mg Every 2 Weeks 
Since there are no laboratory parameters required for entry into Cohort 1 of this study, Screening 
procedures and Day 0 procedures are scheduled for the same day. Patients who qualify for entry into 
Cohort 1 of this study who are currently receiving 800 mg ibalizumab every 2 weeks will have 
physical and laboratory measures performed and receive the first on-study dose of ibalizumab at 
Screening/Day 0 as specified in the Schedule of Events (see Table 3-1). These patients will return to 
the clinic on Day 14 and every 2 weeks thereafter through the remainder of participation in the 
study for study drug administration (800 mg) and effectiveness and safety evaluations. Patients who 
are discontinued or who withdraw from the study prematurely will be asked to return for an Early 
Withdrawal visit to have all assessments detailed in the Schedule of Events for that visit performed. 
 
 
6.1.1 
Screening/Day 0 
Screening and Day 0 (first on-study administration of ibalizumab) are scheduled for the same day. At 
this visit, study information will be reviewed and discussed, and the informed consent form will be 
reviewed and signed by the participant. No procedures, other than a preliminary verbal assessment 
of eligibility by review of inclusion/exclusion criteria, may be done before the informed consent 
process is complete. Once informed consent has been obtained and documented, the following 
procedures may be completed (pre-infusion): 
 
◼ 
Record demographics, medical history (general and HIV), and the patient’s height 
◼ 
Record all prior ART exposure; record all other medications taken within the last 30 
days 
◼ 
Record results of a complete physical examination 
◼ 
Record vital sign measurements 


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◼ 
Record the patient’s weight 
◼ 
Record all AEs that begin after the patient has signed the informed consent (see Section 
8.1 for definitions) 
◼ 
Collect blood and urine for the following laboratory samples: 
– 
Hepatitis serology and C-reactive protein 
– 
Clinical laboratory assessments (serum chemistry, hematology, and urinalysis; see 
Section 7.2.2 for a complete list of parameters) 
– 
Archive sample 
– 
Serum pregnancy test in females of childbearing potential and a follicle-
stimulating hormone (FSH) test in postmenopausal females 
– 
HIV-1 RNA (viral load) 
– 
HIV-1 viral resistance sample (will be stored for later use if needed) 
– 
CD4+ cell count (within 1 hour before the start of the infusion) 
– 
Immunogenicity of ibalizumab 
After the preceding procedures are completed, site personnel will undertake the following (infusion 
and post-infusion): 
 
◼ 
Administer study medication (800 mg) 
◼ 
Record vital sign measurements after the completion of the infusion and observe the 
patient for at least 15 minutes 
◼ 
Record AEs 
 


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6.1.2 
Events for Day 14 (±1 day) and Weeks 4, 6, 8, 10, 14, 16, 18, 20, 
22, 26, 28, 30, 32, 34, 38, 40, 42, 44, 46, 50, 52, 54, 56, 58, 62, 
64, 66, 68, 70, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 98, 100, 
102, 104, 106, 110, 112, 114, 116, 118, 122, 124, 126, 128, 130, 
134, 136, 138, 140, and 142 (±2 days) 
The following will be completed before study drug administration: 
 
◼ 
Record vital sign measurements 
◼ 
Record AEs and concomitant medications 
◼ 
Assess adherence to the OBR (Weeks 4, 8, and 84 only) 
◼ 
Collect urine sample for the following: 
Urine pregnancy test for females of childbearing potential (Weeks 4, 8, 16, 20, 28, 32, 
40, 44, 52, 56, 64, 68, 76, 80, 84, 88, 92, 100, 104, 112, 116, 124, 128, 136, and 140 only) 
Site personnel will undertake the following after administration of study drug (800 mg): 
 
◼ 
Record vital sign measurements after completion of infusion and observe patient for at 
least 15 minutes 
◼ 
Record AEs 
 
6.1.3 
Events for Weeks 12, 24, 36, 48, 60, 72, 96, 108, 120, 132, 
144/EOS and 150/Follow-up (±2 days) 
The following will be completed before study drug administration: 
 
◼ 
Record results of physical examination (complete exam at Weeks 24, 48, 72, 96, 120, 
144, and 150; abbreviated exam at Weeks 12, 36, and 60) 
◼ 
Record the patient’s weight (Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144 and 150 only) 
◼ 
Record vital sign measurements 


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◼ 
Record AEs and concomitant medications 
◼ 
Assess adherence to the OBR 
◼ 
Collect blood and/or urine samples for the following: 
– 
Hepatitis serology and C-reactive protein (Weeks 24, 48,  96, and 150 only) 
– 
Clinical laboratory assessments (serum chemistry, hematology, and urinalysis; See 
Section 7.2.2 for a complete list of parameters)  (Weeks 12, 24, 36, 48, 60, 72, 96, 
120, and 150 only) 
– 
Archive sample (Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, and 150 only) 
– 
Pregnancy test for females of childbearing potential (urine at Weeks 12, 36, 60, 
108, 120, 132, 144, and 150 only); serum at Weeks 24, 48, 72, and 96 only) 
– 
HIV-1 RNA (viral load)  
– 
HIV-1 viral resistance sample (will be stored for later use if needed)  
– 
CD4+ cell count (within 1 hour before the start of the infusion) 
– 
Immunogenicity of ibalizumab (Weeks 24, 48, 72, 96, 120, 144, and 150 only). 
Site personnel will undertake the following after administration of study drug (800 mg) (not done at 
Week 150/Follow-up): 
 
◼ 
Record vital sign measurements after completion of infusion and observe patient for at 
least 15 minutes 
◼ 
Record AEs 
 
6.2 
Cohort 1: 2,000 mg Every 4 Weeks 
Since there are no laboratory parameters required for entry into Cohort 1 of this study, Screening 
procedures and Day 0 procedures are scheduled for the same day. Patients who qualify for entry into 
Cohort 1 of this study who are currently receiving 2,000 mg ibalizumab every 4 weeks will have 
physical and laboratory measures performed and will receive the first on-study dose of ibalizumab at 
Screening/Day 0, as specified in the Schedule of Events (see Table 3-3). These patients will return to 
the clinic at Week 4 and every 4 weeks thereafter through the remainder of participation in the study 


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for study drug administration (2,000 mg) and effectiveness and safety evaluations. Patients who are 
discontinued or who withdraw from the study prematurely will be asked to return for an Early 
Withdrawal visit to have all assessments detailed in the Schedule of Events for that visit performed. 
 
 
6.2.1 
Screening/Day 0 
Screening and Day 0 (first on-study administration of ibalizumab) are scheduled for the same day. At 
this visit, study information will be reviewed and discussed, and the participant will review and sign 
the informed consent form. No procedures, other than a preliminary verbal assessment of eligibility 
by review of inclusion/exclusion criteria, may be done before the informed consent process is 
complete. Once informed consent has been obtained and documented, the following procedures 
may be completed (pre-infusion): 
 
◼ 
Record demographics, medical history (general and HIV), and the patient’s height 
◼ 
Record all prior ART exposure; record all other medications taken within the last 30 
days 
◼ 
Record results of a complete physical examination 
◼ 
Record vital sign measurements 
◼ 
Record the patient’s weight 
◼ 
Record AEs that begin after the patient signs the informed consent (see Section 8.1 for 
definitions) 
◼ 
Collect blood and urine for the following laboratory samples: 
– 
Hepatitis serology and C-reactive protein 
– 
Clinical laboratory assessments (serum chemistry, hematology, and urinalysis; see 
Section 7.2.2 for a complete list of parameters) 
– 
Archive sample 
– 
Serum pregnancy test in females of childbearing potential and an FSH test in 
postmenopausal females 
– 
HIV-1 RNA (viral load) 
– 
HIV-1 viral resistance sample (will be stored for later use if needed) 


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– 
CD4+ cell count (within 1 hour before the start of the infusion) 
– 
Immunogenicity of ibalizumab 
After the preceding procedures are completed, site personnel will undertake the following (infusion 
and post-infusion): 
 
◼ 
Administer study medication (2,000 mg) 
◼ 
Record vital sign measurements after the completion of the infusion and observe the 
patient for at least 15 minutes 
◼ 
Record AEs 
 
 


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6.2.2 
Events for Weeks 4, 8, 16, 20, 28, 32, 40, 44, 52, 56, 64, 68, 76, 
80, 84, 88, 92, 100, 104, 112, 116, 124, 128, 136, and 140 (±2 
days) 
The following will be completed before study drug administration: 
 
◼ 
Assess adherence to the OBR (Weeks 4, 8, and 84 only) 
◼ 
Record vital measurements 
◼ 
Record AEs and concomitant medications 
◼ 
Collect urine sample for the following: 
Urine pregnancy test for females of childbearing potential 
Site personnel will undertake the following after administration of study drug (2,000 mg): 
 
◼ 
Record vital sign measurements after completion of infusion and observe patient for at 
least 15 minutes 
◼ 
Record AEs 
 
6.2.3 
Events for Weeks 12, 24, 36, 48, 60, 72, 96, 108, 120, 132, , 
144/EOS, and 150/Follow-up (±2 days) 
The following will be completed before study drug administration: 
 
◼ 
Record results of physical examination (complete exam at Weeks 24, 48, 72, 96, 120, 
144, and 150 only; abbreviated exam at Weeks 12, 36, and 60 only) 
◼ 
Record the patient’s weight  (Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, and 150 only) 
◼ 
Record vital sign measurements 
◼ 
Record AEs and concomitant medications 
◼ 
Assess adherence to the OBR  
◼ 
Collect blood and/or urine samples for the following: 
– 
Hepatitis serology and C-reactive protein (Weeks 24, 48, 7296, and 150 only) 


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– 
Clinical laboratory assessments (serum chemistry, hematology, and urinalysis; See 
Section 7.2.2 for a complete list of parameters) (Weeks 12, 24, 36, 48, 60, 72, 96, 
120, and 150 only) 
– 
Archive sample (Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, and 150 only) 
– 
Pregnancy test for females of childbearing potential (urine at Weeks 12, 36, 60, 
108, 120, 132, 140, 144, and 150 only; serum at Weeks 24, 48, 72, and 96 only   ) 
– 
HIV-1 RNA (viral load) 
– 
HIV-1 viral resistance sample (will be stored for later use if needed)  
– 
CD4+ cell count (within 1 hour before the start of the infusion) 
– 
Immunogenicity of ibalizumab (Weeks 24, 48, 72, 96, 120, 144, and 150 only) 
Site personnel will undertake the following after administration of study drug (2,000 mg) (not done 
at Week 150/Follow-up): 
 
◼ 
Record vital sign measurements after completion of infusion and observe patient for at 
least 15 minutes 
◼ 
Record AEs 
 
6.3 
Cohort 2 
Patients will complete all Screening procedures during the 6 weeks before Day 0/Baseline. 
Successful Screening results will allow the patients to proceed to the Day 0/Baseline visit, where 
they will initiate the selected OBR in addition to undergoing physical and laboratory measures as 
specified in the Schedule of Events (see Table 3-5). At this visit, patients will also receive the loading 
dose of the study medication (2,000 mg). Patients will return to the clinic on Day 7 for effectiveness 
and safety evaluations and on Day 14 and every 2 weeks thereafter through the remainder of 
participation in the study for study drug administration (800 mg) and effectiveness and safety 
evaluations. Patients who are discontinued or who withdraw from the study prematurely will be 
asked to return for an Early Withdrawal visit to complete all assessments for that visit, as detailed in 
the Schedule of Events. 
 
 


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6.3.1 
Screening (Weeks -6 to -1) 
Screening will begin up to 6 weeks before Day 0. During Screening, study information will be 
reviewed and discussed, and the participant will review and sign the informed consent form. No 
procedures, other than a preliminary verbal assessment of eligibility by review of inclusion/exclusion 
criteria, may be done before the informed consent process is complete. Once informed consent has 
been obtained and documented, the following Screening procedures may be completed: 
 
◼ 
Record demographics, medical history (general and HIV), and the patient’s height 
◼ 
Record all prior ART exposure; record all other medications taken within the last 30 
days 
◼ 
Obtain documentation of HIV-1 infection; if official, signed, written documentation is 
unavailable, then collect a sample for HIV antibody testing as indicated below: 
– 
Obtain documentation of viral resistance, if available (within 6 months of 
Screening), and select an OBR 
– 
Record results of a complete physical examination 
– 
Record vital sign measurements 
– 
Record the patient’s weight 
– 
Record only study-related AEs, which begin once the patient signs the informed 
consent (see Section 8.1 for definitions) 
◼ 
Collect blood and urine for the following laboratory samples: 
– 
Hepatitis serology and C-reactive protein 
– 
Clinical laboratory assessments (serum chemistry, hematology, and urinalysis; see 
Section 7.2.2 for a complete list of parameters) 
– 
Serum pregnancy test in females of childbearing potential and an FSH test in 
postmenopausal females 
– 
HIV-1 RNA (viral load) 
– 
HIV-1 antibody level, if documentation of HIV-1 infection is not provided as 
indicated above 
– 
HIV-1 viral resistance sample (will be stored for later use if needed) 


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– 
CD4+ cell count 
If a patient fails Screening, they may be re-screened one time. 
 
 
6.3.2 
Day 0/Baseline 
The Day 0/Baseline visit may take place at any point during the 4 weeks following the Screening 
Visit. At this visit, patients will receive the first study drug infusion: a loading dose of 2,000 mg. All 
patients must be observed for 1 hour after completion of study drug administration at Baseline. If 
the patient does not experience an AE(s) related to the infusion (local or systemic) through and 
including the second infusion on Day 14, then the observation time can be reduced to 15 minutes 
thereafter. Patients will return to the site every 2 weeks (±2 days) for the remainder of the study to 
receive additional study drug and for effectiveness and safety evaluations. At this visit, the following 
will be completed before study drug administration: 
 
◼ 
Record any changes to ART; record all other medications taken within the 30 days 
before the baseline visit 
◼ 
Record results of a complete physical examination 
◼ 
Record vital sign measurements 
◼ 
Record the patient’s weight 
◼ 
Record only study-related AEs 
◼ 
Collect blood and urine samples for the following: 
– 
Clinical laboratory assessments (serum chemistry, hematology, and urinalysis; see 
Section 7.2.2 for a complete list of parameters) 
– 
Archive sample 
– 
Urine pregnancy test for females of childbearing potential 
– 
HIV-1 RNA (viral load) 
– 
HIV-1 viral resistance sample (will be stored for later use if needed) 
– 
CD4+ cell count (within 1 hour before the start of the infusion) 


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– 
Immunogenicity of ibalizumab 
The patient will also initiate the selected OBR on this day, either at home or in the clinic with site 
personnel supervision. 
After the preceding procedures are completed, site personnel will undertake the following (infusion 
and post-infusion): 
 
◼ 
Administer loading dose of study medication (2,000 mg) 
◼ 
Record vital sign measurements after the completion of the infusion and observe the 
patient for at least 1 hour 
◼ 
Record all AEs 
 
6.3.3 
Events for Day 7 (±1 day) 
Day 7 serves as the time point at which the antiviral activity of ibalizumab will be assessed to address 
the primary effectiveness objective of the study. 
 
Site personnel will undertake the following: 
 
◼ 
Assess adherence to the OBR 
◼ 
Record results of abbreviated physical examination 
◼ 
Record vital sign measurements, AEs, and concomitant medications 
◼ 
Collect blood and urine samples for the following: 
– 
Clinical laboratory assessments (serum chemistry, hematology, and urinalysis; see 
Section 7.2.2 for a complete list of parameters) 
– 
Archive sample 
– 
HIV-1 RNA (viral load) 
– 
HIV-1 viral resistance sample (will be stored for later use if needed) 
– 
CD4+ cell count  
 


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6.3.4 
Events for Day 14 (±1 day), and Weeks 4, 6, 8, 10, 14, 16, 18, 20, 
22, 26, 30, 32, 34, 38, 40, 42, 44, 46, 50, 52, 54, 56, 58, 62, 64, 
66, 68, 70, 74, 76, 78, 80, 82, 86, 88, 90, 92, 94, 98, 100, 102, 
104, 106, 110, 112, 114, 116, 118, 122, 124, 126, 128, 130, 134, 
136, 138, 140, and 142 (±2 days) 
The following will be completed before study drug administration: 
 
◼ 
Record results of physical examination (complete exam at Week 4 only, abbreviated 
exam at Weeks 20, 32, and 40 only)  
◼ 
Record the patient’s weight (Weeks 4, 20, 32, and 40 only) 
◼ 
Record vital sign measurements 
◼ 
Record AEs and concomitant medications 
◼ 
Assess adherence to the OBR (Weeks 4, 8, 20, 32, and 40 only) 
◼ 
Collect urine and perform pregnancy test for females of childbearing potential (Weeks 
4, 8, 16, 20, 32, 40, 44, 52, 56, 64, 68, 76, 80, 88, 92, 100, 104, 112, 116, 124, 128, 136, 
and 140 only)  
◼ 
Collect blood samples for the following: 
– 
HIV-1 RNA (viral load)  (Day 14, and Weeks 4, 6, 8, 16, and 20 only) 
– 
HIV-1 viral resistance sample (will be stored for later use if needed) (Day 14, and 
Weeks 4, 6, 8, 16, and 20 only)  
– 
CD4+ cell count (Day 14,   and Weeks 4, 6, 8, 16, and 20 only) 
Site personnel will undertake the following after administration of study drug (800 mg): 
 
◼ 
Record vital sign measurements after completion of infusion and observe patient for at 
least 1 hour; if the patient did not experience an AE(s) related to the infusion (local or 
systemic) through and including the infusion on Day 14, then the observation time can 
be reduced to 15 minutes 
◼ 
Record AEs  
 


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6.3.5 
Events for Weeks 12, 24, 48, 60, 72, 84, 96, 108, 120, 132, and 
144/EOS (±2 days) 
Site personnel will undertake the following before administration of study drug: 
 
◼ 
Record results of physical examination (complete exam at Week 24, 48, 72, 96, 120, and 
144 only ; abbreviated exam at Weeks 12, 60, and 84 only) 
◼ 
Record the patient’s weight (Weeks 12, 24, 48, 60, 72, 84, 96, 120, and 144 only)  
◼ 
Record vital sign measurements 
◼ 
Record AEs and concomitant medications 
◼ 
Assess adherence to the OBR  
◼ 
Collect blood and/or urine samples for the following: 
– 
Hepatitis serology and C-reactive protein (Weeks 24, 48, and 96, only) 
– 
Clinical laboratory assessments (serum chemistry, hematology, and urinalysis; see 
Section 7.2.2 for a complete list of parameters) (Weeks 12, 24, 48, 60, 72, 84, 96, 
and 120 only) 
– 
Archive sample  (Weeks 12, 24, 48, 60, 72, 84, 96, 120, and 144 only)  
– 
Pregnancy test for females of childbearing potential (serum at Weeks 24, 48, 72, 
and 96 only; urine at all other listed weeks) 
– 
HIV-1 RNA (viral load) 
– 
HIV-1 viral resistance sample (will be stored for later use if needed)  
– 
 
– 
CD4+ cell count (within 1 hour before the start of the infusion) 
– 
Immunogenicity of ibalizumab (Weeks 24, 48, 72, 96, , 120, and 144 only) 
Site personnel will undertake the following after administration of study drug (800 mg): 
 
◼ 
Record vital sign measurements after completion of infusion and observe patient for at 
least 1 hour; if the patient did not experience an AE(s) related to the infusion (local or 
systemic) through and including the second infusion on Day 14, then the observation 
time can be reduced to 15 minutes 


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◼ 
Record AEs 
 
6.3.6 
Events for Weeks 28 and 36 (±2 days)  
The following will be completed before study drug administration: 
 
◼ 
Record the patient’s weight (Week 36 only)  
◼ 
Record vital sign measurements 
◼ 
Record AEs and concomitant medications 
◼ 
Collect blood and/or urine samples for the following: 
– 
Clinical laboratory assessments (serum chemistry, hematology, and urinalysis; see 
Section 7.2.2 for a complete list of parameters) 
– 
Archive sample 
– 
Urine pregnancy test for females of childbearing potential 
– 
HIV-1 RNA (viral load) 
– 
HIV-1 viral resistance sample (will be stored for later use if needed) 
– 
CD4+ cell count (within 1 hour before the start of the infusion) 
Site personnel will undertake the following after administration of study drug (800 mg): 
 
◼ 
Record vital sign measurements after completion of infusion and observe patient for at 
least 1 hour; if the patient did not experience an AE(s) related to the infusion (local or 
systemic) through and including the infusion on Day 14, then the observation time can 
be reduced to 15 minutes 
◼ 
Record AEs 
 
6.3.7 
Events for Week 150/Follow-up Visit (±2 days) (Study drug is not 
administered at this visit) 
The following procedures will be completed at the Week 102/Follow-up visit: 
 


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◼ 
Record results of a complete physical examination 
◼ 
Record the patient’s weight 
◼ 
Record vital sign measurements; 
◼ 
Record AEs and concomitant medications 
◼ 
Assess adherence to the OBR 
◼ 
Collect blood and/or urine samples for the following: 
– 
Hepatitis serology and C-reactive protein 
– 
Clinical laboratory assessments (serum chemistry, hematology, and urinalysis; see 
Section 7.2.2 for a complete list of parameters) 
– 
Archive sample 
– 
Urine pregnancy test for females of childbearing potential 
– 
HIV-1 RNA (viral load) 
– 
HIV-1 viral resistance sample (will be stored for later use if needed) 
– 
CD4+ cell count 
– 
Immunogenicity of ibalizumab 
 
6.4 
Early Withdrawal Procedures 
Patients who withdraw from the study at any time before Week 96/EOS will be asked to complete 
all Early Withdrawal procedures to ensure safety and collect as much effectiveness data as possible.  
 
The following procedures will be completed at the Early Withdrawal visit (study drug is not 
administered at Early Withdrawal): 
 
◼ 
Record results of a complete physical examination 
◼ 
Record the patient’s weight 
◼ 
Record vital sign measurements 


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◼ 
Record AEs and concomitant medications 
◼ 
Assess adherence to the OBR 
◼ 
Collect blood and/or urine samples for the following: 
– 
Hepatitis serology and C-reactive protein 
– 
Clinical laboratory assessments (serum chemistry, hematology, and urinalysis; see 
Section 7.2.2 for a complete list of parameters) 
– 
Archive sample 
– 
Serum pregnancy test for females of childbearing potential 
– 
HIV-1 RNA (viral load) 
– 
HIV-1 viral resistance sample (will be stored for later use if needed) 
– 
CD4+ cell count 
– 
Immunogenicity of ibalizumab 
 
6.5 
Unscheduled Visits 
Unscheduled visits are allowed for the following reasons: 
 
◼ 
To perform a confirmatory plasma viral load determination 
◼ 
To perform confirmatory laboratory testing for clinically abnormal values 
◼ 
Any time the investigator feels that they are clinically required for safety reasons related 
to the patient’s participation in this trial 
Findings during these unscheduled visits must be reported in the EDC system under the 
unscheduled visit section. 
 
 


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7. Study Assessments 
 
A central laboratory will analyze all blood and urine samples with the exception of the HIV-1 
resistance testing and immunogenicity testing, which will be undertaken by appropriate specialty 
contract laboratories. Urine samples will be analyzed at the site; if abnormal results are obtained for 
a patient, a urine sample will be sent to the central laboratory for microscopic evaluation. 
 
The following assessments will be conducted at the times indicated in the Schedule of Events 
(Tables 3-1 through 3-6). 
 
 
7.1 
Activities to Be Completed 
7.1.1 
Demographic Data, Medical History, and Concomitant Medications 
Demographic data, a complete medical history (per patient report), and documentation of prior 
medications will be collected at Screening; information about recent or concomitant medications will 
be obtained at each visit. If the patient is enrolling into Cohort 2, the patient will supply official 
written documentation of HIV-1 infection at Screening, if possible. Otherwise, a sample for an 
HIV-1 antibody test must be collected as part of the Screening procedures. 
 
 
7.1.2 
Complete Physical Examination 
A complete physical examination will include the following organ or body system assessments: head, 
eyes, ears, nose, throat, musculoskeletal, cardiovascular, lymphatic, respiratory, gastrointestinal, skin, 
neurological, and other findings of note. Height and weight will be measured at Screening, and 
weight only will be measured at other times specified. 
 
 


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7.1.3 
Abbreviated Physical Examination 
An abbreviated physical examination will be limited to lymph nodes, respiratory and cardiovascular 
systems, abdomen, extremities, and nervous system and assessment of any specific signs and 
symptoms that the patient reports. 
 
 
7.1.4 
Vital Sign Measurements 
Vital sign measurements will include the patient’s heart rate (beats/minute taken for 1 full minute), 
blood pressure (mm Hg), respiratory rate (breaths/minute taken for 1 full minute), and oral 
temperature (ºC). Measurements will be taken within 1 hour before the start of the infusion and 15 
minutes after the end of the infusion. Blood pressure and heart rate measurements will be obtained 
after the patient has been seated for at least 5 minutes. Ideally, each patient’s blood pressure should 
be measured using the same arm and the same size cuff at each visit. 
 
 
7.2 
Blood and Urine Samples 
7.2.1 
Hepatitis Serology and C-Reactive Protein 
Patients will be screened for hepatitis B (surface antigen) and hepatitis C to determine their hepatitis 
status. 
 
Blood samples will be taken for the analysis of C-reactive protein, which is an inflammatory marker 
whose concentration increases with acute or chronic inflammation. 
 
 
7.2.2 
Clinical Laboratory Parameters 
Collection of blood and urine samples for clinical laboratory assessments will be part of a normal 
safety profile assessment for the study patients. Patients need not fast before blood sampling. 
Samples will be processed using standard procedures as described in the laboratory procedures 
manual and will be analyzed by a central laboratory unless otherwise noted. 
 


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The samples will be analyzed for the following: 
 
◼ 
Hematology: complete white blood cell count with differential, hemoglobin, 
hematocrit, and platelets 
◼ 
Serum chemistry profile: albumin, alkaline phosphatase, alanine aminotransferase 
(ALT), amylase, aspartate aminotransferase (AST), blood urea nitrogen, calcium, 
chloride, creatine phosphokinase, creatinine, direct bilirubin, gamma glutamyl 
transferase, glucose, lactate dehydrogenase, lipase, lipid profile (total cholesterol, high-
density lipoprotein, low-density lipoprotein, and triglycerides), magnesium, phosphorus, 
potassium, sodium, total bilirubin, total protein, and uric acid 
◼ 
Urinalysis: visual inspection for appearance and dipstick assessment for color, pH, 
specific gravity, ketones, protein, glucose, bilirubin, nitrite, urobilinogen, and leukocyte 
esterase 
The urinalysis will be performed at the site by qualified personnel. If the results of the urinalysis are 
abnormal, a urine sample will be sent to the central laboratory for microscopic evaluation. Samples 
will be processed as described in the laboratory procedures manual before being sent to the central 
laboratory for evaluation. 
 
Tests with Grade 3 or Grade 4 abnormal results should be repeated within 72 hours of the site 
becoming aware of the abnormal value(s). See Appendix B for details and definitions of toxicities. 
The Principal Investigator should discuss any Grade 3 or 4 abnormal laboratory results with the 
medical monitor/Sponsor for appropriate patient disposition, including potential withdrawal from 
the study (see Section 5.3.1 for additional information). Per Section 5.3.1, the study treatment should 
be stopped for all Grade 3 or 4 treatment-related laboratory abnormalities, as defined in Appendix 
B. Any patient with a Grade 3 or Grade 4 laboratory abnormality that resolves before the next 
scheduled dose may have the study drug reinstituted. If a patient develops a persistent Grade 3 or 
Grade 4 treatment-emergent laboratory abnormality, excluding triglycerides and cholesterol, that 
does not resolve prior to the next scheduled study drug administration, study drug may be 
discontinued. Patients with Grade 3 or 4 triglyceride and/or cholesterol elevations are allowed to 
continue to receive study drug. 
 
 
7.2.3 
Archive Sample 
A separate blood sample will be taken and stored for possible research use. 


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7.2.4 
Serum Follicle-Stimulating Hormone Testing 
A serum FSH test will be performed on postmenopausal females at Screening (see Section 8.7). The 
level of FSH should exceed 35 IU/L for the patient to be considered postmenopausal. If the patient 
does not meet this criterion, she must agree to use proper birth control precautions as described in 
Section 8.7 and must have serum and urine pregnancy tests throughout the protocol at times 
specified in the Schedule of Events. 
 
 
7.2.5 
Pregnancy Testing 
A serum pregnancy test will be performed at Screening, EOS, Early Withdrawal and other defined 
visits for all females of childbearing potential. A urine pregnancy test will be performed at other 
defined study visits to confirm that a female has not become pregnant during the study. These tests 
are performed for the protection and safety of the fetus, as the risk to the fetus is unknown. Any 
patient who becomes pregnant during the study will be withdrawn from the study. See Section 8.7 
for a description of procedures to be followed in case of pregnancy. 
 
 
7.2.6 
HIV-1 RNA Level 
Blood samples for viral load will be used to determine the effectiveness of the study regimens and 
should be drawn before infusion during visits that include an infusion. 
 
 
7.2.7 
HIV-1 Viral Resistance Testing 
Blood samples for HIV-1 viral resistance testing should be collected before the start of the infusion 
at the indicated visits. Viral resistance testing will include assessments of reverse transcriptase, 
protease, integrase and envelope genes, and chemokine coreceptor utilization; the samples will be 
collected and stored, and testing will only be performed for patients who experience virologic failure 
while on the study.  
 


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Collected and stored samples may also be used for the TrofileTM Assay, a blood test that identifies 
the tropism of a patient’s HIV strain (i.e., R5, X4, or a combination). The results show whether the 
patient is infected with the virus that enters cells using the R5 co-receptor, the X4 co-receptor, or 
both. 
 
 
7.2.8 
CD4+ Cell Count 
Blood samples for CD4+ cell count will be collected over the course of the study to determine how 
well the immune system is functioning. In most patients infected with HIV, an increase in the 
number of CD4+ cells is an indicator of the effectiveness of antiretroviral medication. 
 
If a patient experiences toxicity, defined as two consecutive laboratory results, at least 14 days apart, 
with a CD4+ cell count below 200 cells/mm3 that also represents a 50% reduction from the baseline 
CD4+ cell count, the patient will be discontinued from the study. 
 
 
7.2.9 
Immunogenicity of Ibalizumab 
Blood samples will be collected to test for the development of antibodies against ibalizumab at Day 
0, EOS, Early Withdrawal, and other defined visits. Samples will be collected prior to ibalizumab 
infusion if an infusion is scheduled for that visit. The incidence of anti-ibalizumab antibody 
production will be determined using a validated enzyme-linked immunosorbent assay (ELISA) that 
has been validated for the detection of anti-ibalizumab antibodies in human serum even if circulating 
drug is present. Additional samples may be collected when clinical observations suggest the 
possibility of a clinically significant anti-ibalizumab immune response (e.g., allergic response, serum 
sickness, low drug levels, and/or loss of virologic response). 
 
 
8. Adverse Events 
 
8.1 
Definitions 
Per the FDA regulations in 21 CFR 312.32, the following definitions apply to this protocol: 


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Adverse Events. An AE is defined as any untoward medical occurrence associated with the use of a 
drug in humans, whether or not considered drug related. 
 
Adverse Reaction. Any AE caused by a drug. 
 
Treatment-Emergent AEs. A TEAE is defined as any event not present before exposure to study 
drug or any event already present that worsens in either intensity or frequency following exposure to 
test medication. 
 
Serious Adverse Event or Serious Suspected Adverse Reaction. An AE or suspected adverse 
reaction is considered ‘‘serious’’ if, in the view of either the investigator or Sponsor, it results in any 
of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of 
existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions, or a congenital anomaly/birth defect. Important medical events that 
may not result in death, be life-threatening, or require hospitalization may be considered serious 
when, based upon appropriate medical judgment, they may jeopardize the patient or subject and may 
require medical or surgical intervention to prevent one of the outcomes listed in this definition. 
 
Suspected Adverse Reaction. A suspected adverse reaction means any AE for which there is a 
reasonable possibility that the drug caused the AE. For the purposes of IND safety reporting, 
“reasonable possibility” means there is evidence to suggest a causal relationship between the drug 
and the AE. 
 
Unexpected Adverse Event or Unexpected Adverse Reaction. This term refers to an AE or 
adverse reaction that is not listed in the investigator’s brochure or is not listed at the specificity or 
severity that has been observed. 
 
 
8.2 
Eliciting Adverse Event Information 
At every study visit, patients will be asked a standard, nondirective question, such as “How have you 
been feeling since your last visit?” to elicit any medically related changes in their well-being. They 
will also be asked if they have been hospitalized, had any accidents, used any new medications, or 
changed concomitant medication regimens (both prescription and over-the-counter medications). 


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In addition to patient self-report, AEs will be documented from clinically significant findings 
resulting from abnormal laboratory test values, physical examination findings, or other documents 
that are relevant to patient safety.  
 
 
8.3 
Reporting Adverse Events 
The investigator is responsible for reporting to the Sponsor or designee all AEs that are observed or 
reported by the patient during the study (from the time the patient signs informed consent until 30 
days after the last dose of study medication is given), regardless of their relationship to study drug or 
their clinical significance. Patients will be instructed to contact study site personnel at any time after 
informed consent if any symptoms develop. 
 
To ensure compliance with FDA regulations (21 CR 312.64), site investigators must immediately 
report to the Sponsor all AEs that meet the SAE criteria, regardless of presumed relationship to the 
investigational agent. The Sponsor will carefully review the SAE information to monitor the 
investigational drug’s toxicity profile and patient safety. If any event meets the FDA’s reporting 
criteria, it will be submitted to the FDA as an IND Safety Report (21 CFR 312.32). 
 
Recording of AEs will begin after study drug is first administered. Any untoward medical condition 
that occurs after the informed consent is signed but before the first administration of the study drug 
will be recorded as medical history, unless it is related to a study procedure. AEs will be recorded 
from the first dose of study medication and until 30 days after the last dose of study medication, 
regardless of its relationship to study drug. AEs will be documented in the patient’s source 
documents and recorded in the AE section of the EDC system. 
 
All AEs reported or observed during the study must be recorded in detail in the AE section of the 
EDC system and followed to a satisfactory resolution or until the Principal Investigator deems the 
event to be chronic or the patient to be stable. 
 
Information to be collected includes the event term, date of onset, date of resolution, Investigator-
specified assessment of severity and relationship to study drug, and seriousness, as well as any 
required treatment or evaluations and outcome. 
 


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Pre-existing conditions (present before the start of the AE collection period) are considered 
concurrent medical conditions and should NOT be recorded as AEs. However, if the pre-existing 
condition worsens in severity, the investigator must report it as an AE. 
 
Each AE should be recorded to represent a single diagnosis. Accompanying signs (including 
abnormal laboratory values) or symptoms should NOT be recorded as additional AEs. If a diagnosis 
is unknown, sign(s) or symptom(s) should be recorded as an AE(s). Changes in laboratory values are 
only considered to be AEs if they are judged to be clinically significant (i.e., if some action or 
intervention is required or if the investigator judges the change to be beyond the range of normal 
physiological fluctuation). If abnormal laboratory values are the result of pathology for which there 
is an overall diagnosis (e.g., increased creatinine in renal failure), the diagnosis only should be 
recorded as an AE. 
 
Pre-planned procedures (surgeries or therapies) that were scheduled prior to the start of AE 
collection are not considered AEs. However, if a pre-planned procedure is performed early (e.g., as 
an emergency) due to a worsening of the pre-existing condition, the worsening of the condition 
should be captured as an AE. Elective procedures performed where there is no change in the 
patient’s medical condition should not be recorded as AEs, but should be documented in the 
patient’s source documents. 
 
The Medical Dictionary for Regulatory Activities (MedDRA) and WHO Drug Dictionary 
(WHODD) will be used to code all AEs and classify all medicines, respectively. All coding will be 
performed by Westat and will be reviewed and approved by the medical monitor. 
 
All AEs, whether serious or not, should be followed to a satisfactory resolution or until the Principal 
Investigator deems the event to be chronic or the patient to be stable and the AE is determined to 
be not clinically significant. 
 
 
8.4 
Assessment of Causality 
The investigator’s assessment of an AE’s relationship to study drug is part of the documentation 
process, but it is not a factor in determining what is or is not reported in the study. If there is any 
doubt as to whether a clinical observation is an AE, the event should be reported. 
 


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The relationship or association of the study drug in causing or contributing to the AE will be 
characterized by the investigator using the following classifications and criteria: 
 
Unrelated. This relationship suggests that there is no association between the study drug and the 
reported event. To be deemed unrelated, an alternative etiology must be present. 
 
Possible. This relationship suggests that treatment with the study drug caused or contributed to the 
AE. That is, the event follows a reasonable temporal sequence from the time of drug administration 
and/or follows a known response pattern to the study drug, but could also have been produced by 
other factors. 
 
Probable. This relationship suggests that a reasonable temporal sequence of the event with drug 
administration exists and—based upon the known pharmacological action of the drug, known or 
previously reported adverse reactions to the drug or class of drugs, or judgment based on the 
investigator’s clinical experience—the association of the event with study drug administration seems 
likely. 
 
Definite. This relationship suggests that a definite causal relationship exists between the drug 
administration and the AE and that other conditions (concurrent illness, progression/expression of 
disease state, or concurrent medication reaction) do not appear to explain the event. 
 
 
8.5 
Assessment of Severity 
The intensity of the AE will be rated by the investigator as mild, moderate, severe, or potentially life-
threatening using the following criteria: 
 
Mild (Grade 1): Symptoms causing no or minimal interference with usual social and functional 
activities. 
 
Moderate (Grade 2): Symptoms causing greater than minimal interference with usual social and 
functional activities. 
 
Severe (Grade 3): Symptoms causing inability to perform usual social and functional activities. 
 


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Potentially Life-Threatening (Grade 4): Symptoms causing inability to perform basic self-care 
functions OR medical or operative intervention indicated to prevent permanent impairment, 
persistent disability, or death. 
 
Details for grading severity are given in Appendix B. Changes in the severity of an AE should be 
documented to allow an assessment of the duration of the event at each level of intensity to be 
performed. AEs characterized as intermittent require documentation of onset and duration of each 
episode. 
 
 
8.6 
Serious Adverse Event Reporting 
Any AE considered serious by the Principal Investigator according to the previously described 
criteria must be reported using the Westat SAE Report Form and submitted to the Westat 
Regulatory Affairs Department via fax or email within 24 hours of the site becoming aware of the 
event. Site staff must alert Westat of incoming safety information via the Westat SAE Hotline, either 
prior to or immediately after faxing/emailing the SAE Form. 
 
SAE Hotline:  888-464-5246 
SAE Fax: 
888-865-1983 
Email:  
Regulatory@Westat.com 
 
SAE reports must be supported by source documents. Key information that must be supported by 
source documents includes: 
 
◼ 
Event term 
◼ 
Onset date 
◼ 
Event management 
◼ 
Relatedness of the event to the study drug 
◼ 
Changes in study drug dosage, including suspension or discontinuation 
◼ 
If judged not study drug-related, an alternate etiology 
◼ 
Resolution date 


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When reporting an SAE to Westat, a thorough summary of the event should be provided, including 
copies of related documentation. Before submission of these documents to Westat, all patient 
identifiers must be obliterated; the documents must be labeled only with the patient’s identification 
number to safeguard the patient’s privacy. 
 
Supplemental source documentation related to the SAE may include: 
 
◼ 
Clinic and/or hospitalization records 
◼ 
Laboratory reports 
◼ 
Pathology reports 
◼ 
Surgical reports 
◼ 
Other test results, such as ECGs, x-rays, lumbar punctures, and computed tomography 
(CT) scans 
◼ 
Consult notes 
◼ 
Hospital admission and discharge summary 
◼ 
Death certificate 
◼ 
Autopsy report 
When an SAE results in hospitalization or prolongation of an existing hospitalization, a copy of the 
hospital admission and discharge summaries and any pertinent laboratory or diagnostic reports 
should be faxed to Westat as soon as they become available. Similarly, documentation of the cause 
of death (e.g., an autopsy report or death certificate) should be submitted to Westat when a death is 
reported. 
 
The investigator should report to Westat any change in the initial SAE Report information or 
additional information that becomes available after the initial SAE Report submission. Each follow-
up SAE Report should be numbered sequentially. 
 
The Sponsor or designee will notify the FDA and all participating Principal Investigators in an IND 
safety report about potential serious risks, from clinical trials and any other source, no later than 15 
days in the following cases: 
 


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◼ 
Serious and unexpected suspected adverse reactions, only if there is evidence to suggest 
a causal relationship between the drug and the AE 
◼ 
Findings from other studies, such as epidemiological studies, pooled analysis of multiple 
studies, or clinical studies that suggest a significant risk in humans exposed to the drug 
◼ 
Findings from animal or in vitro testing: Any finding from animal or in vitro testing, 
whether or not conducted by the Sponsor, that suggest a significant risk in humans 
exposed to the drug, such as reports of mutagenicity, teratogenicity, or carcinogenesis or 
reports of organ toxicity 
◼ 
Increased rate of occurrence of serious suspected adverse reactions. Any clinically 
important increase in the rate of serious suspected adverse reactions over that listed in 
the protocol or investigator’s brochure must also be reported 
The Sponsor or designee will notify the FDA and all participating Principal Investigators of any 
unexpected fatal or life-threatening suspected adverse reaction as soon as possible but no later than 
7 calendar days after the initial receipt of the information. The investigators will follow their 
institutional policies of reporting safety information to the institutional review board (IRB). They 
will provide copies of the correspondence with the ethics committee (EC) to the Sponsor or 
designee for filing. 
 
 
8.7 
Pregnancy 
Sexually active men who have partners of childbearing potential and all females of childbearing 
potential must use an effective method of birth control (e.g., oral contraceptives, double-barrier 
methods, hormonal injectable, implanted contraceptives, or vasectomy) during the study and for 30 
days after the last dose of study drug is administered. 
 
Childbearing Potential. Females of childbearing potential are female patients who are not 
surgically sterile (no history of bilateral tubal ligation, hysterectomy, or bilateral salpingo-
oophorectomy), are not postmenopausal (at least 1 year without menses), and are not otherwise 
sterile by medical evaluation. These patients must use an adequate form of birth control as 
determined by the investigator. Spermicidals are considered one component of a double-barrier 
method. Complete abstinence from sexual intercourse will suffice without additional contraceptive 
measures. However, it is recommended that the Principal Investigator discuss all options with these 
female patients and instruct that if the patient becomes sexually active, she must use appropriate 
contraceptive measures. 


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Similarly all men who become sexually active during the study with a partner of childbearing 
potential must be instructed to use appropriate contraceptive measures. 
 
Sterile or Postmenopausal. Females who are surgically sterile or postmenopausal will also be 
eligible for the study. Postmenopausal is defined as having had no menses for at least 12 months and 
having an FSH level above 35 IU/L for reproductive-age females. A surgically sterile status is 
defined as having a history of bilateral tubal ligation, hysterectomy, or bilateral salpingo-
oophorectomy. 
 
Suspected Pregnancy. During the study, all females of childbearing potential will be instructed to 
contact the investigator immediately if they suspect they might be pregnant (e.g., late or missed 
menstrual period). Male patients will be instructed to contact the investigator if a sexual partner 
suspects she may be pregnant. 
 
If a patient or investigator suspects that the patient may be pregnant before study drug 
administration, the study drug must be withheld until the results of laboratory pregnancy testing are 
available. If pregnancy is confirmed, the patient must not receive the study drug and must be 
withdrawn from the study. The investigator must immediately notify the medical monitor of a 
pregnancy associated with study drug exposure and record the event on the Pregnancy Surveillance 
Form that will be provided to each site. Protocol-required procedures for study discontinuation 
must be performed on the patient unless contraindicated by pregnancy (e.g., x-ray studies). Other 
appropriate follow-up procedures should be considered if indicated. 
 
The investigator must follow up with a pregnant patient or the pregnant partner of any sexually 
active male patient every 4 weeks while the woman is pregnant and every 4 weeks thereafter to 
follow perinatal and neonatal outcome. The investigator must report follow-up information 
regarding the course of the pregnancy, including perinatal and neonatal outcome, on the appropriate 
Pregnancy Surveillance Form. Infants who result from such pregnancies should be followed for a 
minimum of 8 weeks for safety assurances. 
 
Pregnancy Surveillance Forms will be submitted to the Westat Regulatory Affairs Department via 
the SAE fax line. HHS encourages the reporting of all in utero exposures to antiretroviral agents to 
the Antiretroviral Pregnancy Registry (telephone 800-258-4263 or fax 800-800-1052). 
 


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9. Statistical Considerations 
 
9.1 
General Methodology 
The data collected are intended primarily for clinical review and interpretation. The analysis of study 
data will be primarily descriptive, with emphasis on tabular and graphical displays. Descriptive 
statistics will be used to guide decisions as to the clinical relevance of findings. Unless otherwise 
stated, p-values will be determined only if they appear to be warranted from the summary statistics. 
 
For continuous data, descriptive statistics will be presented as number of patients (n), mean, 
standard deviation, median, minimum, and maximum. For categorical data, the frequency and 
percentage of patients in each category will be presented. Percentages will be based on non-missing 
data unless otherwise specified. 
 
Data will be described and analyzed using the SAS System Version 9.3 or later (SAS Institute Inc., 
Cary, NC, SAS System). Individual patient data will be presented in patient data listings. 
 
 
9.2 
Populations for Analysis 
9.2.1 
Efficacy Populations 
9.2.1.1 
Intent-to-Treat Population 
The ITT population is defined as all patients enrolled into the study. Patient disposition will be 
based on the ITT population. The ITT Analysis Population will be used for the primary analysis at 
Day 7. Patients with missing effectiveness data at Day 7 will have their effectiveness set to failure for 
all dichotomous effectiveness variables. This will be referred to as the MEF analysis. 
 
 


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9.2.1.2 
Modified Intent-to-Treat Population 
The modified intent-to-treat (mITT) population is defined as all ITT patients who received at least 
one dose of study drug. The mITT Analysis Population will be used for a supportive effectiveness 
analysis and will include all data without imputing values for missing data.  
 
 
9.2.2 
Safety Population 
All patients who receive at least one partial dose of study drug will be included in the safety dataset 
for analysis (SAF) population. Patients will be analyzed according to the treatment they actually 
received. The safety population will be used for the safety analyses. 
 
 
9.3 
Patient Disposition 
Study completion data will be summarized for all enrolled patients. The number and percentage of 
patients who complete treatment, discontinue study medication prematurely, or discontinue the 
study prematurely, will be tabulated. The primary reason for premature discontinuation of study 
medication and/or discontinuation from study participation will be tabulated. Any additional 
reason(s) for premature discontinuation of study medication will also be tabulated. A listing of all 
enrolled patients will be provided. 
 
 
9.4 
Definition of Baseline 
For patients in Cohort 1 who were enrolled in the TMB-202 or TMB-301 studies, Baseline values 
for TMB-311 are defined as the values recorded for the Baseline visit in the previous study. For 
patients in Cohort 1 who were not enrolled in the TMB-202 or TMB-301 studies, Baseline values for 
TMB-311 are defined as the last values recorded prior to receiving the first dose of ibalizumab. For 
patients in Cohort 2, Baseline is defined as the Day 0 visit of TMB-311 (this study). 
 
 


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9.5 
Demographics and Baseline Characteristics 
Descriptive statistics will be presented for demographic and other baseline characteristics for the 
ITT and mITT populations. Medical history and medication history findings will be listed and 
summarized. 
 
 
9.6 
Exposure to Study Medication 
Duration of treatment will be presented for the mITT population. 
 
 
9.7 
Safety Analyses 
The safety analyses will include descriptions of TEAEs, Class C events per the CDC Classification 
System for HIV Infection, clinical laboratory test results, physical examination findings, vital sign 
results, and ibalizumab antibody levels (immunogenicity of ibalizumab). 
 
 
9.7.1 
Adverse Events 
The incidence (n and %) of AEs, SAEs, and early termination of study medication or study 
participation due to an AE will be presented. Additionally, AEs will be tabulated according to 
severity and relatedness categories as reported by the investigator. AEs will be presented in tables 
organized alphabetically by Preferred Term within System Organ Class. Each patient will be counted 
only once for each AE reporting level. 
 
 
9.7.2 
Clinical Safety Laboratory Parameters 
Clinical laboratory parameters will be presented by visit. Descriptive statistics will be used to 
summarize observed values by visit as well as the change from Baseline at each visit. Clinical 
laboratory values outside the normal ranges will be flagged in patient data listings. Non-numeric data 
will be presented in patient data listings, but will not be tabulated. 
 


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9.8 
Efficacy 
The primary efficacy endpoint (Cohort 2 only) is the proportion of patients achieving a ≥0.5 log10 
decrease in viral load from Baseline to Day 7 along with a 95% confidence interval around the 
observed rate. 
 
Secondary effectiveness endpoints (Cohort 2) include: 
 
◼ 
Proportion of patients with HIV-1 RNA levels <50 copies/mL and <400 copies/mL at 
assessment time points 
◼ 
Mean change from Baseline in viral load at Day 7 and all assessment time points  
◼ 
Proportion of patients achieving a ≥0.5 log10 and ≥1.0 log10 decrease from Baseline in 
viral load at all assessment time points 
Exploratory statistical analyses will explore changes in HIV-1 drug sensitivity/susceptibility to 
determine relationships with protocol-defined virologic failure after ibalizumab administration in 
combination with the OBR.  
 
 
10. Data Handling and Quality Assurance 
 
10.1 
Electronic Case Report Forms 
An EDC will be used to capture data electronically for this trial, meaning that all data will be entered 
in the EDC system from source documents at the investigational site. Case report forms (CRFs) will 
be developed to be used as worksheets. Completion of these worksheets is optional. 
 
A patient ID list will be maintained separately from the research records and will not be recorded or 
stored with the CRFs. 
 
All data must be entered in English. The EDC system should always reflect the latest observations 
on the patients participating in the trial. Therefore, the data are to be entered into the EDC as soon 
as possible during or after the patient’s visit. To avoid inter-observer variability, every effort should 


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be made to ensure that the same individual who made the initial baseline determinations completes 
all antiviral activity/safety evaluations. The clinical site monitor will verify that all data entries in the 
EDC system are accurate and correct. If some assessments have not been done, or if certain 
information is not available, not applicable, or unknown, the investigator should indicate this in the 
EDC system. The investigator will be required to sign off on the clinical data. 
 
The Sponsor or designee will review the EDC system and evaluate the entries for completeness and 
consistency. The clinical site monitor will compare the data captured in the EDC system with the 
source documents to ensure there are no discrepancies between critical data recorded in the EDC 
system and the source documents. All entries, corrections, and alterations are to be made by the 
responsible investigator or his/her designee. The clinical site monitor cannot enter data in the EDC 
system. Once clinical data in the EDC system have been submitted, corrections to the data fields will 
be marked by an audit trail, meaning that the reason for the change, the name of the person who 
performed the change, and the time and date of the change will be logged. Roles and rights of the 
site personnel responsible for entering the clinical data into the EDC system will be determined in 
advance and documented on the appropriate form. 
 
If additional corrections are needed, the responsible clinical site monitor or project data manager will 
raise a query in the EDC application. The appropriate investigational staff will answer queries sent to 
the investigator. This correspondence will be marked by an audit trail by the EDC application, 
meaning that the name of investigational staff and the time and date stamp are captured for each 
interaction/revision. 
 
 
10.2 
Monitoring of the Study 
The purpose of clinical site monitoring is to ensure that the trial is conducted in an ethically sound 
and scientifically rigorous manner. Specifically, sites will be carefully monitored by the Sponsor or 
designee to ensure that (1) the rights and well-being of participants are protected; (2) data are 
complete, accurate, and verifiable; and (3) the trial is conducted in compliance with the protocol, 
applicable government regulations (e.g., US FDA, Taiwan Food and Drug Administration [TFDA]), 
the ICH E6(R1): Guidelines for Good Clinical Practice, local IRB policies, and current standard 
operating procedures at the sites), and the Sponsor/Sponsor’s representative. 
 


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The clinical site monitor, as a representative of the Sponsor, formally evaluates the accuracy and 
completeness of the data collected and assesses compliance with the relevant regulations and 
policies. In doing so, the clinical site monitor will visit the Principal Investigator and study facility 
periodically, in addition to maintaining necessary telephone, email, or letter contact. The clinical site 
monitor will maintain current personal knowledge of the study through observation, review of study 
records and source documentation, and discussion of the conduct of the study with the Principal 
Investigator and staff. 
 
Each investigator is expected to make a reasonable effort to accommodate the clinical site monitor 
when site visits are necessary. Because this trial is utilizing an EDC system, the monitor will need to 
access the data entry computer and internet during the visit. 
 
 
10.3 
Inspection of Records 
Principal Investigators and institutions involved in the study will permit trial-related monitoring, 
audits, IRB review, and regulatory inspection(s) by providing direct access to all study records. In the 
event of an audit, the Principal Investigator agrees to allow the Sponsor, representatives of the 
Sponsor, the US FDA, or other relevant regulatory authorities access to all study records. 
 
The Principal Investigator should immediately notify the Sponsor or designee of any audits 
scheduled by any regulatory authorities and promptly forward, to the Sponsor or designee, copies of 
any audit reports received. 
 
 
10.4 
Study Record Retention 
Essential documents should be retained for at least 2 years after the last approval of a marketing 
application in an ICH region (or longer if mandated by the local IRB). Moreover, they should be 
retained until there are no pending or contemplated marketing applications in an ICH region or at 
least 2 years have elapsed since the formal discontinuation of clinical development of the 
investigational product. However, if required by the applicable regulatory requirements or by an 
agreement with the Sponsor, these documents should be retained for a longer period. It is the 
responsibility of the Sponsor or designee to inform the Principal Investigator or institution as to 
when these documents no longer need to be retained. 


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11. Administrative Considerations 
 
The following administrative items are meant to guide the Principal Investigator in the conduct of 
the trial but may be changed based on industry and government standard operating procedures, 
working practice documents, or guidelines. Any changes in trial procedures will be reported to the 
IRB, but will not necessarily result in a protocol amendment. 
 
 
11.1 
Confidentiality 
All laboratory specimens, evaluation forms, reports, and other records will be identified in a manner 
designed to maintain patient confidentiality. All records will be kept in a secure storage area with 
limited access. Clinical information will not be released without the written permission of the patient 
(or the patient’s guardian), except as necessary for monitoring and auditing by the Sponsor, its 
designee, the US FDA or applicable regulatory authorities, or the IRB. 
 
The Principal Investigator and all employees and coworkers involved with this study may not 
disclose or use for any purpose, other than performance of the study, any data, record, or other 
unpublished confidential information disclosed to those individuals for the purpose of the study. 
Prior written agreement from the Sponsor or designee must be obtained for the disclosure of any 
said confidential information to other parties. 
 
 
11.2 
Institutional Review Board or Independent Ethics 
Committee Approval 
Federal regulations and the ICH guidelines require that approval be obtained from an IRB/EC 
before participation of human patients in research studies. Before the study onset, the protocol, 
informed consent, advertisements to be used for patient recruitment, and any other written 
information regarding this study to be provided to the patient or the patient’s legal guardian must be 
approved by the IRB/EC. Documentation of all IRB/EC approvals and of the IRB/EC compliance 


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with ICH E6(R1), US FDA, TFDA, and other applicable regulatory authorities will be maintained by 
the site and available for review by the Sponsor or designee. 
 
The Principal Investigator is responsible for obtaining continued review of the clinical research at 
intervals specified by the IRB, but not exceeding 1 year. The Principal Investigator must supply the 
Sponsor or designee with written documentation of continued review of the clinical research. 
 
 
11.3 
Modification of the Protocol 
This protocol will be implemented as approved by the IRB, and no changes will be implemented 
prior to IRB approval except those necessary to remove an apparent immediate hazard to the 
patient. Amendments to the protocol must be approved by the IRB prior to implementation. 
 
 
11.4 
Informed Consent 
A signed informed consent form, in compliance with Title 21 of the US Code of Federal 
Regulations (CFR) Part 50 and in accordance with other regulations for non-US sites, will be 
obtained from each patient before any study-related procedures are performed and any personal 
information is collected. An informed consent template may be provided to investigative sites by the 
Sponsor or designee. The consent must be reviewed by the Sponsor or designee before IRB 
submission if the site proposes or makes any institution-specific modifications to study-related 
procedures, the risk language, or any other significant changes that would alter the information 
relayed. Once reviewed, the consent will be submitted by the Principal Investigator to his/her IRB 
for review and approval before the start of the study. If the informed consent form is revised during 
the course of the study, all active participating patients must sign the revised IRB-approved consent 
form. 
 
Before enrollment, each prospective patient will be given a full explanation of the study and allowed 
to read the approved informed consent form. The information given should be in a language or 
manner that is easily understandable to the participant or legal guardian. Once the Principal 
Investigator is assured that the patient/legal guardian understands the implications of participating 
in the study and has been given the proper time to consider whether to participate or not, the 


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patient/legal guardian will be asked to give consent to participate in the study by signing the 
informed consent form. The Principal Investigator will also sign the form at that time. 
 
The Principal Investigator will provide a copy of the signed informed consent form to the patient 
and/or legal guardian. The original form will be maintained in the patient’s medical records at the 
site. 
 
 
11.5 
Protocol Violations and Deviations 
A deviation from the protocol is an unintended and/or unanticipated departure from the procedures 
and/or processes that were approved by the Sponsor and the IRB, and that were agreed to by the 
Principal Investigator. Deviations usually have an impact on individual patients or a small group of 
patients and do not involve inclusion/exclusion or primary endpoint criteria. A protocol violation 
occurs when (1) there is non-adherence to the protocol that results in significant additional risk to 
the patient, (2) the patient or Principal Investigator has failed to adhere to significant protocol 
requirements (e.g., inclusion/exclusion criteria), or (3) there is non-adherence to FDA regulations 
and/or ICH E6(R1) guidelines. 
 
For this protocol, violations will be defined as exceptions to the inclusion or exclusion criteria, 
situations where a patient is required to withdraw but the investigator believes the patient should 
remain in the study, and the use of an excluded concomitant medication. All other departures from 
the protocol (e.g., missed visit windows, laboratory samples not collected on the required day) will 
be documented as protocol deviations. The Principal Investigator or designee must document and 
explain any protocol deviation or violation in the patient’s source documentation. The investigator 
should notify the IRB of all protocol violations and deviations per local institutional policy. Protocol 
deviations and violations will be documented by the responsible clinical site monitor during 
monitoring visits, and those observations will be reviewed with the investigator. 
 
The Principal Investigator may implement a change from the protocol without prior Sponsor and 
IRB approval only to eliminate an immediate hazard to a patient. The implemented change should 
be submitted to the IRB for review as soon as possible. 
 
If the investigator believes that an exception to the protocol is justified for an individual patient, the 
investigator may present the facts and rationale to the medical monitor and request a one-time 


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exception. This request will be submitted in writing on a protocol inquiry form, which will be faxed 
to the medical monitor for review and disposition. The medical monitor will then fax the decision to 
the investigator regarding approval or denial of the request. This written documentation must be 
filed in the investigator’s study file. 
 
This process will apply if the investigator believes that a patient should receive an excluded 
concomitant medication and remain in the study, or if the investigator believes that a patient should 
remain in the study when the protocol dictates that the patient should be discontinued. The 
implemented change should be submitted to the IRB for review as soon as possible. However, it is 
the policy of the Sponsor that there will be no exceptions granted concerning the inclusion and 
exclusion criteria. 
 
 
11.6 
Study Reporting Requirements 
By participating in this study, the Principal Investigator agrees to submit reports of AEs according to 
the timeline and method outlined in the protocol. In addition, the Principal Investigator agrees to 
submit periodic reports to his/her IRB as appropriate. 
 
 
11.7 
Financial Disclosure and Obligations 
Principal Investigators and subinvestigators are required to provide financial disclosure information 
to allow the Sponsor or designee to submit the complete and accurate certification or disclosure 
statements required under Title 21 CFR 54. In addition, the Principal Investigator and 
subinvestigators must provide the Sponsor or designee with a commitment to update this 
information promptly, if any relevant changes occur during the course of the investigation and for 1 
year following the completion of the study. 
 
The Sponsor or designee is not financially responsible for further testing/treatment of any medical 
condition that may be detected during the Screening process. In addition, in the absence of specific 
arrangements, the Sponsor or designee is not financially responsible for treatment of the patient’s 
disease. 
 
 


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11.8 
Investigator Documentation 
Before beginning the study, the Principal Investigator will be asked to comply with ICH E6(R1) 8.2, 
Title 21 CFR, and other applicable regulatory requirements by providing the essential documents to 
the Sponsor or designee, which include but are not limited to the following: 
 
◼ 
An original Investigator-signed investigator agreement page of the protocol 
◼ 
Documentation of IRB approval of the protocol and informed consent 
◼ 
The IRB-approved informed consent, samples of site advertisements for recruitment 
for this study, and any other written information regarding this study that is to be 
provided to the patient or legal guardians. 
◼ 
A Form FDA 1572, fully executed, and all updates on a new fully executed Form FDA 
1572. 
◼ 
Curricula vitae for the Principal Investigator and each subinvestigator listed on Form 
FDA 1572. A copy of the current license must be provided. The curricula vitae must be 
signed and dated by the Principal Investigators and subinvestigators within 1 year before 
study start-up to indicate that the documents are accurate and current. 
◼ 
Completed financial disclosure forms to allow the Sponsor or designee to submit 
complete and accurate certification or disclosure statements required under Title 21 
CFR 54. In addition, the investigators must provide to the Sponsor or designee with a 
commitment to update this information promptly if any relevant changes occur during 
the course of the investigation and for 1 year following the completion of the study 
(Section 11.7). 
◼ 
Laboratory certifications and normal ranges for any local laboratories used by the site, in 
accordance with Title 42 CFR 493. 
 
11.9 
Study Conduct 
The Principal Investigator agrees that the study will be conducted according to the principles of ICH 
E6(R1), the principles of the World Medical Association Declaration of Helsinki, and regulatory 
requirements of the US FDA and TFDA. The Principal Investigator will conduct all aspects of this 
study in accordance with all national, state, and local laws or regulations. 
 
 


TAIMED BIOLOGICS, INC. 
CONFIDENTIAL 
PROTOCOL: TMB-311 
DATE: 11 DECEMBER 2017 
 
 
Use or disclosure of data contained on this page is subject  
to the restriction on the title page of this proposal or quotation. 
98 
 
 
 
11.10 Publications 
Following completion of the study, the data may be considered for reporting at a scientific meeting 
or for publication in a scientific journal. In these cases, the Sponsor or designee will be responsible 
for these activities and will work with the investigators to determine how the manuscript is written 
and edited, the number and order of authors, the publication to which it will be submitted, and 
other related issues. The Sponsor has final approval authority over all such issues. 
 
Data are the property of the Sponsor and cannot be published without prior authorization from the 
Sponsor. 
 
A description of this clinical trial (study) will be available on http://clinicaltrials.gov, as required by 
US law. 
 
 
 
 


TAIMED BIOLOGICS, INC. 
CONFIDENTIAL 
PROTOCOL: TMB-311 
DATE: 11 DECEMBER 2017 
 
 
Use or disclosure of data contained on this page is subject  
to the restriction on the title page of this proposal or quotation. 
99 
 
 
 
References 
 
 
1 Gardner, E.M., McLees, M.P., Steiner, J.F., Del Rio, C., and Burman, W.J. (2011). The 
spectrum of engagement in HIV care and its relevance to test-and-treat strategies for 
prevention of HIV infection. Clinical Infectious Diseases, 52(6):793-800. 
2 U.S. Centers for Disease Control and Prevention. (2011). HIV prevalence estimates—United 
States. Morbidity and Mortality Weekly Report, 60(47):1618-1623. 
3 Panel on Antiretroviral Guidelines for Adults and Adolescents. (2014). Guidelines for the use of 
antiretroviral agents in HIV-1-infected adults and adolescents. Washington, DC: U.S. Department of 
Health and Human Services. 
4 Schwartzberg, L.S., Stepanski, E.J., Fortner, B.V., and Houts, A.C. (2008). Retrospective chart 
review of severe infusion reactions with rituximab, cetuximab, and bevacizumab in community 
oncology practices: Assessment of clinical consequences. Supportive Cancer Care, 16:393-398. 
5 Dillman, R.O. (1999). Infusion reactions associated with the therapeutic use of monoclonal 
antibodies in the treatment of malignancy. Cancer and Metastasis Reviews, 18:465-471. 
6 Dalakas, M.C. (2004). The use of intravenous immunoglobulin in the treatment of autoimmune 
neuromuscular disease: Evidence-based indications and safety profile. Pharmacology and 
Therapeutics, 102:177-193. 
7 Schwartzberg, L.S., Stepanski, E.J., Fortner, B.V., and Houts, A.C. (2008). Retrospective chart 
review of severe infusion reactions with rituximab, cetuximab, and bevacizumab in community 
oncology practices: Assessment of clinical consequences. Supportive Cancer Care, 16:393-398. 
 

SAP_001.pdf: 
WESTAT 
An Employee-Owned Research Corporation 
 
 
  
 
 
TaiMed Biologics, Inc. 
 
 
 
Protocol TMB-311 
NCT02707861 
 
A Phase 3, Multicenter, Expanded Access Study of Ibalizumab Plus an Optimized Background 
Regimen (OBR) in Treatment-Experienced Patients Infected With Multi-Drug Resistant (MDR) 
HIV-1 
 
 
Statistical Analysis Plan 
August 17, 2018 
Final Version 3 
 
 
TaiMed Biologics, Inc 
2 Executive Circle, Suite 280 
Irvine, CA 92614 
 
Prepared By: 
Ken Gerald, PhD 
Director of Biostatistics 
 
Jennifer Fulton, MS 
Biostatistician 
 
 
Westat 
5615 Kirby Drive, Suite 710 
Houston, TX 77005 
 
 
CONFIDENTIAL 


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Table of Contents 
Statistical Analysis Plan ..................................................................................................................... 1 
1. Introduction ..................................................................................................................................... 3 
2. Study Overview .............................................................................................................................. 3 
2.1. Study Design ....................................................................................................................................... 3 
2.2. Study Objectives .................................................................................................................................. 4 
2.2.1. 
Primary .................................................................................................................................. 4 
2.2.2. 
Secondary............................................................................................................................... 5 
2.3. Study Drug Dosage and Administration ............................................................................................... 5 
2.4. Procedures ........................................................................................................................................... 6 
2.4.1. 
Patient Identification .............................................................................................................. 6 
2.4.2.  
Randomization ...................................................................................................................... 6 
2.4.3.  
Blinding/Unblinding .............................................................................................................. 6 
2.4.4.  
Replacement .......................................................................................................................... 6 
3. Statistical Analysis Considerations ................................................................................................... 6 
3.1. Sample Size ......................................................................................................................................... 6 
3.2. Analysis Populations ............................................................................................................................ 6 
3.2.1. 
Intent-to-Treat (ITT) Population ............................................................................................. 6 
3.2.2.  
Safety (SAF) Population ........................................................................................................ 7 
3.3. Data Handling ...................................................................................................................................... 7 
3.3.1. 
Measurement Times ............................................................................................................... 7 
3.3.2.  
Clinical Laboratory Data Handling Conventions .................................................................... 7 
3.3.3.  
Baseline Values ..................................................................................................................... 7 
3.3.4.  
Missing Data Conventions ..................................................................................................... 8 
3.4. Statistical Methods ............................................................................................................................... 8 
3.4.1.  
General Overview and Plan of Analysis ................................................................................. 8 
3.4.2.  
Hypothesis Testing ................................................................................................................ 9 
4. Statistical Analysis ........................................................................................................................... 9 
4.1. Patient Disposition ............................................................................................................................... 9 
4.2. Demographic and Physical Characteristics ........................................................................................... 9 
4.3. Analysis of Safety and Tolerability .................................................................................................... 10 
4.3.1.  
Extent of Study Drug Exposure ........................................................................................... 10 
4.3.2.  
AEs ..................................................................................................................................... 10 
4.3.3.  
Clinical Laboratory Parameters............................................................................................ 11 
4.3.4.  
Vital Signs ........................................................................................................................... 12 
4.3.5.  
Physical Examination Findings ............................................................................................ 12 
4.3.6.  
Medications ......................................................................................................................... 12 
4.4. Efficacy ............................................................................................................................................. 13 
4.5.1.   
Primary Efficacy Endpoint ................................................................................................. 13 
4.5.2.  
Secondary Efficacy Endpoints ............................................................................................. 13 
4.5.3.  
Graphical Displays .............................................................................................................. 16 
4.6. Exploratory/Other Analyses ............................................................................................................... 16 
5. References ...................................................................................................................................... 16 
6. Proposed Summary Listings and Tables ......................................................................................... 17 


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1. Introduction 
 
This document outlines the planned statistical analyses for data collected within the scope 
of the TaiMed ibalizumab protocol TMB-311, entitled “A Phase 3, Multicenter, 
Expanded Access Study of Ibalizumab Plus an Optimized Background Regimen (OBR) 
in Treatment-Experienced Patients Infected With Multi-Drug Resistant (MDR) HIV-1”. 
This statistical analysis plan (SAP) applies to the most recent version of the study 
protocol (dated 11 December 2017) and will be updated as necessary if future protocol 
amendments warrant an update to the manner of analysis. This document was prepared in 
accordance with the International Conference on Harmonisation (ICH) Guideline E3: 
Structure and Content of Clinical Study Reports [1]. 
 
2. Study Overview 
 
2.1. Study Design  
 
This Phase 3 multicenter study will evaluate safety and tolerability of ibalizumab in 
HIV positive patients with MDR HIV infection. Eligible patients will include those 
currently receiving ibalizumab under a TaiMed-sponsored or Investigator-
INDprotocol, and treatment-experienced patients with no history of ibalizumab 
treatment who are on a failing regimen, or who have failed and are off treatment. 
Patients will be enrolled in one of two Cohorts. Cohort 1 consists of patients currently 
receiving ibalizumab via other TaiMed-sponsored or Investigator-IND 
(compassionate use) protocols. These patients will continue their current dosage of 
ibalizumab (800 mg every 2 weeks or 2000 mg every 4 weeks). Cohort 2 consists of 
patients initiating ibalizumab. These patients will receive a 2000 mg loading dose at 
Baseline/Day 0 followed by 800 mg maintenance doses every 2 weeks.  
 
For Cohort 1, screening procedures and Day 0 procedures are scheduled for the same 
day. Patients who qualify for entry into Cohort 1 of this study who are currently 
receiving 800 mg ibalizumab every 2 weeks will have physical and laboratory 
measures performed and receive the first on-study dose of ibalizumab at 
Screening/Day 0. These patients will return to the clinic on Day 14 and every 2 weeks 
thereafter through the remainder of participation in the study (up to 144 weeks) for 
study drug administration (800 mg) and effectiveness and safety evaluations. Patients 
who are discontinued or who withdraw from the study prematurely will be asked to 
return for an Early Withdrawal visit to have all assessments detailed in the Schedule 
of Events for that visit performed. 
 
Patients who qualify for entry into Cohort 1 of this study who are currently receiving 
2000 mg ibalizumab every 4 weeks will have physical and laboratory measures 
performed, and receive the first on-study dose of ibalizumab at Screening/Day 0. 
These patients will return to the clinic at Week 4 and every 4 weeks thereafter 
through the remainder of participation in the study (up to 144 weeks) for study drug 
administration (2000 mg) and effectiveness and safety evaluations. Patients who are 
discontinued or who withdraw from the study prematurely will be asked to return for 


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an Early Withdrawal visit to have all assessments detailed in the Schedule of Events 
for that visit performed. 
 
For Cohort 2, patients will complete all screening procedures during the six weeks 
before Baseline/Day 0. Successful screening results will allow the patients to proceed 
to the Baseline/ Day 0 Visit, where they will initiate the selected OBR in addition to 
undergoing physical and laboratory measures. At this visit patients will also receive 
the loading dose of the study medication (2000 mg). Patients will return to the clinic 
on Day 7 for effectiveness and safety evaluations, and on Day 14 and every two 
weeks thereafter through the remainder of participation in the study (up to 144 weeks) 
for study drug administration (800 mg) and effectiveness and safety evaluations. 
Patients who are discontinued or who withdraw from the study prematurely will be 
asked to return for an Early Withdrawal visit to have all assessments detailed in the 
Schedule of Events for that visit performed.   
 
All patients who complete Week 144 or end of study (EOS) visit will return for a 
follow-up visit at Week 150.  Patients may be discontinued from the study at the 
patient’s request or if the patient becomes pregnant, at investigator request, for a 
protocol violation, for treatment-related serious or intolerable adverse events (AEs), 
for toxicity (defined as two consecutive laboratory results, at least 14 days apart, with 
a CD4+ T-cell count below 200 cells/mm3 that also represents a 50% reduction from 
the Baseline CD4+ T-cell count), or for virologic failure.  Virologic failure is defined 
as two consecutive measurements beginning at Week 24 or later if less than a 0.5 
log10 decline from the Baseline viral load.  
 
 
2.2. Study Objectives 
 
2.2.1. 
Primary  
 
The primary objectives of this study are to: 
 
Cohort 1 
• Continue to provide ibalizumab to patients currently receiving ibalizumab 
treatment under Investigator-sponsored INDs or TaiMed-sponsored protocols 
• Demonstrate the safety and tolerability of ibalizumab in HIV positive 
patients with MDR HIV infection 
Cohort 2 
• Provide access to ibalizumab for qualifying MDR HIV-1 infected patients 
with limited treatment options 
• Demonstrate the safety, efficacy, and tolerability of ibalizumab in HIV 
positive patients with MDR HIV infection 


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2.2.2. 
Secondary 
 
The secondary objectives of this study are to: 
 
• Demonstrate the antiviral activity of ibalizumab in HIV positive patients with 
MDR HIV infection 
 
• Characterize HIV-1 sensitivity/susceptibility changes associated with 
protocol-defined virologic failure after ibalizumab administration in 
combination with OBR 
 
• Determine the presence and significance of anti-ibalizumab antibodies 
associated with protocol-defined virologic failure after ibalizumab 
administration, if any (immunogenicity of ibalizumab) 
 
 
2.3. Study Drug Dosage and Administration 
 
The investigational product, ibalizumab, is a humanized IgG4 monoclonal antibody 
(MAb) administered via intravenous (IV) infusion.  Patients will be enrolled in one of 
two Cohorts (Cohort 1 and Cohort 2). Cohort 1 patients will continue their current 
dosage of ibalizumab (800 mg every 2 weeks or 2000 mg every 4 weeks). Cohort 2 
patients will receive a 2000 mg loading dose at Baseline/Day 0 followed by 800 mg 
maintenance doses every 2 weeks. 
 
Patients receiving ibalizumab under Investigator-IND protocols, who will enroll into 
Cohort 1 of this study, are currently being supplied with ibalizumab vials containing a 
1.2 mL injection volume and 180 mg ibalizumab per vial. For this study, these 
patients will continue receiving ibalizumab in this vial configuration until that supply 
of drug product is exhausted, at which time they will be switched to the drug product 
with a 1.33 mL injection volume and 200 mg ibalizumab per vial. 
 
Patients receiving ibalizumab in study TMB-301, who will enroll into Cohort 1 of this 
study, and patients initiating ibalizumab in Cohort 2 will receive only vials with a 
1.33 mL injection volume and 200 mg ibalizumab per vial. During this study, it will 
be very important to ensure that all drug supplies are clearly labeled and segregated 
by vial configuration to prevent confusion.  
 
In addition to the study drug, all patients will receive an OBR, which is a standard–
of-care regimen selected by the investigator based upon treatment history and the 
results of recent viral resistance testing. For patients enrolling into Cohort 2, previous 
resistance testing done within 6 months prior to Screening must demonstrate that the 
patient’s viral isolate is sensitive/susceptible to a minimum of one of the agents 
selected for the OBR. The patient must be willing and able to take at least one of the 
agents to which their virus is sensitive/susceptible as part of the OBR. 
 


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2.4. Procedures 
 
2.4.1. 
Patient Identification 
 
Once consent is obtained and study eligibility has been determined, a 
patient will be enrolled into the study and will be assigned a Participant 
Identification (PID) number. The 5-digit PID number will consist of a 2-
digit site number and a 3-digit sequential patient number. If a patient in 
Cohort 2 is a screen failure, the PID number will not be reassigned. 
 
2.4.2.  
Randomization 
 
This will be an open-label, non-randomized study. 
 
2.4.3.  
Blinding/Unblinding 
 
There will be no blinding/unblinding considerations for this open-label, 
non-randomized study. 
 
2.4.4.  
Replacement 
 
Patients who withdraw or otherwise discontinue the study prematurely 
will not be replaced.   
 
3. Statistical Analysis Considerations 
 
3.1. Sample Size  
 
Anticipated enrollment is approximately 100 patients from approximately 50 sites in 
North America; however, the numbers of participating patients and sites will not be 
limited and may exceed 100 patients.   
 
3.2. Analysis Populations 
 
3.2.1. 
Intent-to-Treat (ITT) Population 
 
The ITT population is defined as all patients enrolled into the TMB-311 
study. The ITT Analysis Population will be used for the patient 
disposition, demographic and physical characteristics, and efficacy 
analyses. 
 
If there are ITT patients who do not receive at least one complete dose of 
study drug, then a modified ITT (mITT) Analysis Population will be used 
for a supportive effectiveness analysis.  
 


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3.2.2.  
Safety (SAF) Population 
 
All patients who receive at least one partial dose of study drug will be 
included in the SAF Population. Patients will be analyzed according to the 
treatment they actually received. The SAF Population will be used for the 
safety analyses. 
 
 
3.3. Data Handling 
 
3.3.1. 
Measurement Times 
 
The nominal visit time point entered on the electronic case report forms 
(eCRFs) will be used.  Patients are asked to adhere to the following visit 
schedule (with windows in parentheses): 
• For Cohort 1 patients, Screening and Day 0 (first on-study 
administration of ibalizumab) are scheduled for the same day. 
• For Cohort 2 patients, the Screening will occur 1 to 6 weeks prior to 
Day 0. 
• For Cohort 2, Day 7 (+/- 1 day) serves as the time point at which the 
antiviral activity of ibalizumab will be assessed to address the primary 
effectiveness objective. 
• For all Cohorts, Day 14 (+/- 1 day) and Week 4 (+/- 2 days) through 
Week 144/EOS Visit (+/- 2 days) from the Day 0 date (Visit Week 
will depend on the dosing schedule per Cohort 1 or 2; please refer to 
the Schedule of Visits Tables 3.1-3.6 in the study protocol). 
 
3.3.2.  
Clinical Laboratory Data Handling Conventions 
 
If a patient has multiple results in the clinical laboratory data for the 
Screening visit, only the last result prior to the first dose of study drug will 
be included in the analysis.  If a patient has multiple results (retests) for 
subsequent visits, the retest results will only be included in the analysis if 
the patient does not have a value recorded for the original assessment at 
the given visit. 
 
3.3.3.  
Baseline Values 
 
For patients in Cohort 1 who were enrolled in the TMB-202 or TMB-301 
studies, Baseline values for TMB-311 are defined as the values recorded 
for the Baseline visit in the previous study. For patients in Cohort 1 who 
were not enrolled in the TMB-202 or TMB-301 studies as well as for 
patients in Cohort 2, Baseline is defined as the last assessment prior to 
their first dose of study drug on the TMB-311 Day 0 visit.  
 


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3.3.4.  
Missing Data Conventions 
 
Cohort 2 patients with missing data at Day 0 will use the Screening visit 
value as their Day 0 result. Similarly, patients with missing data at 
Screening will use the Day 0 visit value as their Screening result. No 
Screening or Day 0 data will be imputed for Cohort 1 patients.  
 
Unless otherwise specified, missing data for subsequent visits will be 
considered missing at random and will not be imputed. If necessary, 
imputation of partial dates may be performed during the data analysis and 
will be documented (e.g., missing month=July; missing day=15).  
 
The Missing Equals Failure (MEF) imputation technique will be applied 
to the viral load measures (log10 copies/mL and copies/mL) only. If a viral 
load measurement is missing at any scheduled visit, the value will be 
replaced with the baseline viral load measurement. Also, all visits after a 
confirmed virologic failure will be imputed as failures (replaced with the 
baseline measurement) for all study visits even if the patient discontinued 
early.  
 
The Last Observation Carried Forward (LOCF) imputation technique 
will be applied to the CD4+ T-Cell Counts (cells/mm3 ) only.  If a CD4+ 
T-Cell Count is missing at any scheduled visit, the value will be replaced 
with the most recent previous non-missing value. 
 
 
3.4. Statistical Methods 
 
3.4.1.  
General Overview and Plan of Analysis 
 
The data collected are intended primarily for clinical review and 
interpretation. The analysis of study data will be primarily descriptive, 
with emphasis on tabular and graphical displays. Descriptive statistics will 
be used to guide decisions as to the clinical relevance of findings. Unless 
otherwise stated, p-values will be determined only if they appear to be 
warranted from the summary statistics. 
 
All results will be displayed in the following patient groupings: 
 
1) Cohort 1 TMB-301 rollover patients; 
2) Cohort 1 TMB-202 rollover patients in the 800mg dose group; 
3) Cohort 1 TMB-202 rollover patients in the 2000mg dose group; 
4) Cohort 2 patients; 
5) Total – includes all patients from 1-4. 
 
The two patients who were formerly enrolled in the investigator-sponsored 
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For continuous data, descriptive statistics will be presented as number of 
patients (n), mean, standard deviation, median, minimum and maximum. 
For categorical data, the frequency and percentage of patients in each 
category will be presented. Percentages will be based on non-missing data 
unless otherwise specified. 
 
Data will be described and analyzed using the SAS System Version 9 
(SAS Institute Inc., Cary, NC, SAS System). Individual patient data will 
be presented in patient data listings. 
 
3.4.2.  
Hypothesis Testing  
 
This study is designed to evaluate the safety and efficacy of ibalizumab in 
treatment-experienced patients infected with multi-drug resistant HIV-1.  
No formal statistical hypothesis testing is planned for the study. [Note: 
Hypothesis testing may be performed as additional/exploratory analyses 
(see Section 4.6)]. 
 
4. Statistical Analysis 
 
 
4.1. Patient Disposition 
 
The number of patients in the ITT and SAF Populations will be tabulated.  
 
Study completion data will be summarized for all enrolled patients. The number and 
percent of patients who complete treatment; discontinue study medication 
prematurely; or discontinue the study prematurely will be tabulated. The primary 
reason for premature discontinuation of study medication and/or discontinuation 
from study participation will be tabulated. Any additional reason(s) for premature 
discontinuation of study medication will also be tabulated. A listing of all enrolled 
patients will be provided. 
 
4.2. Demographic and Physical Characteristics 
  
Summary statistics will be presented for demographic and other Baseline 
characteristics for the ITT Population. Tabulations for age, sex, ethnicity 
(Hispanic/Latino, Neither Hispanic nor Latino, Unknown), and race (American 
Indian/Alaska Native, Asian, Black/African American, Native Hawaiian/Other 
Pacific Islander, White, Unknown, or Other) will be presented. Age (years) will be 
calculated as the integer part of [(date of screening - date of birth + 1)/365.25]. 
Baseline physical characteristics, such as height (cm) and weight (kg), will also be 
summarized.  
 
A listing of demographic and Baseline characteristics will be presented, as well as a 
listing of medical history. 


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4.3. Analysis of Safety and Tolerability 
 
Safety and tolerability will be assessed by both clinical and laboratory examinations. 
Summary statistics will be presented by AEs; hematology and chemistry; vital signs, 
changes from Baseline, and clinically significant findings; and abnormal physical 
examination findings in the SAF Population. Clinical laboratory values outside the 
normal ranges will be flagged in patient data listings. Non-numeric data will be 
presented in patient data listings, but will not be tabulated. 
  
4.3.1.  
Extent of Study Drug Exposure  
 
Summary statistics will be presented for the cumulative dose (mg) and 
duration of treatment received by the patients in the SAF Population. 
Duration of treatment will be represented as number of days from first 
dose of study drug. For Cohort 1 patients, the date of their first dose of 
study drug in the previous study will be used. Corresponding listings will 
also be generated for study drug administration and OBR adherence.  
 
4.3.2.  
AEs   
 
All AEs will be coded, using MedDRA dictionary version 17.0. The use of 
another version will not be considered a violation of the SAP, nor require 
an amendment to the plan. All summary tables will be based on coded 
preferred terms (PTs), instead of verbatim terms. The only exception being 
all rashes are combined into one category named RASHES. The categories 
and definitions of severity and causal relationship for all AEs, including 
the criteria for which an AE is to be classified as “serious,” are as 
described in the protocol (Section 8). 
 
A treatment-emergent AE (TEAE) is defined as any event not present 
before exposure to study drug or any event already present that worsens in 
either intensity or frequency following exposure to study drug. AEs with 
missing start dates, but with stop dates either overlapping into the dosing 
period or missing, will be considered TEAEs. A TEAE with missing 
severity or relationship will be considered severe or related, respectively.  
 
The overall incidence of TEAEs will be summarized for all patients in the 
SAF Population. The number and percentage of patients having the 
following will be tabulated: 
• TEAE 
• Serious TEAE 
• TEAE leading to discontinuation 
• TEAE with outcome of death 
• TEAE related to study drug (definitely, probably, or possibly) 


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• Severe TEAE 
• Class C TEAE per the Centers for Disease Control and Prevention 
(CDC) Classification System for HIV Infection 
 
The overall incidence of TEAEs will also be summarized by System 
Organ Class (SOC), and by SOC and PT. The number and percentage of 
patients reporting an event, as well as the number of events reported by the 
patients will be tabulated. The incidence of serious TEAEs and TEAEs 
leading to study discontinuation (if any) will be summarized in the same 
manner. If there are multiple occurrences of the same TEAE within any 
SOC or PT for the same patient, only the first occurrence will be counted.  
 
The incidence of TEAEs by severity/grade (mild, moderate, severe, or 
potentially life-threatening) and by relationship to study drug (unrelated, 
possibly related, probably related, and definitely related), and the 
incidence of SAEs by relationship to study drug, will also be summarized.  
 
All other AEs will be classified as non-TEAEs and identified in listings 
only.  Serious TEAEs, TEAEs leading to study discontinuation, and 
TEAEs with an outcome of death will be presented in separate listings, if 
needed.  
 
These tables will be repeated for patients receiving an investigational 
agent [Fostemsavir (BMS-068), Cabotegravir, or PRO140] as a 
concomitant medication versus those patients who did not receive an 
investigational agent.  
  
 
4.3.3.  
Clinical Laboratory Parameters 
 
Summary statistics will be presented for laboratory measurements 
(hematology and chemistry) overall for all patients in the SAF Population. 
Urinalysis results will be presented in a listing.  The following analytes 
will be tabulated/listed:  
• Hematology: complete white blood cell count with differential, 
hemoglobin, hematocrit, and platelets.  
• Serum chemistry profile: albumin, alkaline phosphatase, alanine 
aminotransferase (ALT), amylase, aspartate aminotransferase (AST), 
blood urea nitrogen, calcium, chloride, creatine phosphokinase, 
creatinine, direct bilirubin, gamma glutamyl transferase, glucose, 
lactate dehydrogenase, lipase, lipid profile (total cholesterol, high-
density lipoprotein, low-density lipoprotein, and triglycerides), 
magnesium, phosphorus, potassium, sodium, total bilirubin, total 
protein, and uric acid. In addition, eGFR will be presented using the 
following formula:  eGFR = 1.86 x [Creatinine/88.4]-1.154 x [Age]-0.203 
x [0.742 if female] x [1.210 if Black]. 


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Urinalysis results will be presented in a data listing and will include results 
from microscopic testing only. Pregnancy test, Serum Follicle-Stimulating 
Hormone (FSH) test, Hepatitis Serology, C-reactive Protein, and Viral 
Resistance Testing will also be presented in a data listing only.   
 
Normal ranges for the laboratory parameters will be provided by the 
laboratory that performed the assessments. All normal ranges will be 
standardized and results will be reported in standard units. The tables will 
include summary statistics for the Baseline assessments and the changes 
from Baseline to each subsequent time point of measurement. A listing of 
patients with abnormal (i.e., outside normal range) laboratory assessments 
will also be presented.   
 
Potentially Clinically Significant (PCS) criteria may be applied to 
laboratory parameters as clinically indicated, and if applied, will be 
summarized as described above. PCS is defined as a laboratory value that 
is lower or higher than a laboratory’s normal range limits.  
 
Note: Electronic clinical laboratory data will be received at Westat. Data 
reconciliation will be performed to resolve any discrepancies with the 
Oracle database. Details of data receipt will be described in the Data 
Receipt Plan.  
 
4.3.4.  
Vital Signs 
 
Summary statistics for vital signs and weight will be presented overall for 
all patients in the SAF Population for all scheduled visits. Actual values 
and changes from Baseline will be summarized for all visits where 
collected.  
 
4.3.5.  
Physical Examination Findings   
 
Physical examination findings at each scheduled visit will be summarized 
overall for all patients in the SAF Population. The number and percent of 
patients with abnormal findings by body system will be tabulated.   
 
4.3.6.  
Medications 
 
All prescriptions or over-the-counter medications continued at the start of 
the trial or started during the trial, and different from the study drug will 
be recorded. All of these medications will be coded, using WHO Drug 
Dictionary (March 2014). The use of another version will not be 
considered a violation of the SAP, nor require an amendment to the plan. 
Both the coded terms and verbatim terms will be presented in data listings 
for: 
• Concomitant procedures (procedures are not coded) 


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• Previous and Concomitant medications  
• OBR medications 
• ART medications 
 
 
4.4. Efficacy 
 
 
As described in section 3.3.3 of this document, the MEF technique will be applied to 
the efficacy analyses with regard to imputing missing viral load results as applicable.  
Note:  Prior to calculating change from Baseline in viral load, the log10 value of each 
measurement will be calculated and will be rounded to one decimal point. 
 
 
4.5.1.   
Primary Efficacy Endpoint 
 
Per the protocol, the primary efficacy endpoint for the Cohort 2 patients is 
defined as the proportion of patients achieving a ≥ 0.5 log10 decrease in 
viral load from Baseline at Day 7 on study drug. A 95% confidence 
interval around the observed rate will be presented.  This endpoint will be 
presented for all Cohort 2 patients, as well as stratified by: 
 
1) Sex (Male vs Female) 
2) Age (<50 vs  > 50) 
3) Race (Caucasian, Asian, and Other) 
 
The primary efficacy endpoint will not be analyzed for the TMB-301 and 
TMB-202 rollover patients, as they did not have dosing or viral load 
measurements at Day 7 on study drug in the TMB-311 study.   
 
4.5.2.  
Secondary Efficacy Endpoints 
 
Although the TMB-311 protocol indicates the secondary efficacy 
endpoints would only be performed for the Cohort 2 patients, for 
completeness all secondary efficacy endpoints will be assessed for all 
patients in all cohorts at applicable visits. 
 
4.5.2.1 HIV-1 RNA levels (copies/mL) 
 
The frequency and proportion of patients achieving RNA levels < 50 
copies/mL and < 400 copies/mL along with 95% confidence intervals 
around the observed rate will be presented at all key visits [Day 7 (Cohort 
2 only), and Weeks 24, 48, 72, 96, 120, and 144/EOS] where assessed.  
 


TaiMed Biologics, Inc. 
Protocol TMB-311 
 
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Page 14 of 53 
Summary statistics for the actual and change from Baseline of RNA levels 
will be presented for at all visits where assessed.   
4.5.2.2 Viral Load (log10 copies/mL) 
 
The frequency and proportion of patients achieving a ≥ 0.5 log10 and ≥ 1.0 
log10 decrease from Baseline in viral load along with 95% confidence 
intervals will be performed at all key visits [Day 7 (Cohort 2 only), and 
Weeks 24, 48, 72, 96, 120, and 144/EOS] where assessed. The mean 
change from Baseline at all assessment time points will be presented.  
 
These tables will be repeated for patients receiving an investigational 
agent [Fostemsavir (BMS-068), Cabotegravir, or PRO140] as a 
concomitant medication versus those patients who did not receive an 
investigational agent.   
 
4.5.2.3 Virologic Outcome 
 
Snapshot Approach 
Virologic outcome will be assigned for each patient at each key visit after 
Week 12 [Weeks 24, 48, 72, 96, 120, and 144/EOS], per the snapshot 
approach, using the following standard categories: 
 
1=Virologic success ( 0.5 log10 decline from Baseline in viral load) 
2a=(<0.5 log10 copies/mL drop from Baseline in viral load) 
2b=Discontinued efficacy portion of study because of virologic failure 
(may still continue safety) 
2c=Discontinued because of other reasons and the drop from baseline  
in viral load at the time of discontinuation was <0.5 log10 copies/mL 
2d=OBR changed  
3a=Discontinued because of AE or death 
3b=Discontinued because of other reasons and the drop from baseline  
in viral load at the time of discontinuation was >=0.5 log10  
copies/mL 
3c=Missing data during the window but on study 
 
Other Virologic Outcomes 
Other virologic outcomes will also be defined as follows: 
 


TaiMed Biologics, Inc. 
Protocol TMB-311 
 
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Page 15 of 53 
Failure to achieve/maintain response:          
Patient does not have 0.5 log10 decline from baseline (BL) by Week 12 
on study drug OR patient has a 0.5 log10 decline from BL prior to Week 12 
but fails to maintain the 0.5 log10 decline from BL and does not have a 1 
log10 increase from nadir on any two consecutive scheduled efficacy 
assessments after achieving the 0.5 log10 decline from BL. 
 
Rebound:  
 
Patient has a 0.5 log10 decline from BL by Week 12 but viral load 
remains >=50 copies (not suppressed), followed by 1 log10 increase from 
nadir at two consecutive scheduled visits any time after achieving the 0.5 
log10 decline from BL. 
 
Breakthrough:  
 
Patient has suppressed viral load (< 50 copies) at any time after primary 
endpoint followed by 200 copies at two consecutive scheduled efficacy 
assessments. 
 
Suboptimal Response:  
 
Patient has a 0.5 log10 decline but does not suppress (<50 copies) at any 
time after primary endpoint and does not have a 1 log10 increase from 
nadir on any two consecutive scheduled efficacy assessments after 
achieving the 0.5 log10 decline from BL. 
 
Virologic Suppression:  
 
Patient has a 0.5 log10 decline and does suppress (<50 copies) at any time 
after primary endpoint and does not have a 1 log10 increase from nadir on 
any two consecutive scheduled efficacy assessments after achieving the 
0.5 log10 decline from BL. 
 
A table summarizing virologic outcome at the each key visit after Week 
12 [Weeks 24, 48, 72, 96, 120, and 144/EOS] according to the above 
categories will be provided.  A listing indicating the virologic outcome for 
each patient will be included.  
 
 
4.5.2.4 CD4+ T-Cell Counts 
 
Summary statistics will be presented for CD4+ T-cell count and change 
from Baseline in CD4+ T-cell count at the each key visit after Week 12 
[Weeks 24, 48, 72, 96, 120, and 144/EOS]. 
 
CD4+ T-Cell Counts for all patients at all assessed visits will also be 
presented in a data listing. The listing will include a column indicating 
whether or not the patient met the definition of toxicity (2 consecutive 
laboratory results, at least 14 days apart, with a CD4+ T-cell count below 


TaiMed Biologics, Inc. 
Protocol TMB-311 
 
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Page 16 of 53 
200 cells/mm3 that also represents a 50% reduction from the Baseline 
CD4+ T-cell count). 
 
 
4.5.3.  
Graphical Displays 
 
In addition to the tables and listings described above, the following 
graphical displays of efficacy endpoints will also be included: 
• Proportion of patients achieving a ≥ 0.5 log10 decrease from Baseline 
in viral load at all scheduled visits; 
• Proportion of patients achieving a ≥ 1.0 log10 decrease from Baseline 
in viral load at all scheduled visits; 
• Proportion of patients achieving RNA levels < 50 copies/mL at all 
scheduled visits;  
• Proportion of patients achieving RNA levels < 400 copies/mL at each 
study visit;  
• Mean (+/- SE) RNA levels (copies/mL) at all scheduled visits;  
• Mean (+/- SE) change from Baseline in RNA levels (copies/mL) at all 
scheduled visits;  
• Mean (+/- SE) CD4+ cell count (cells/mm3) at all scheduled visits;  
• Mean (+/- SE) change from Baseline in CD4+ T-cell count 
(cells/mm3) at all scheduled visits. 
 
4.6. Exploratory/Other Analyses 
 
Summaries of viral resistance test results, immunogenicity results, and other 
virology results will be presented, prepared by TaiMed. 
 
 
5. References 
 
1. Center for Drug Evaluation and Research, Food and Drug Administration, U.S. Department of Health and 
Human Services. (2013, June). Guidance for industry: Human immunodeficiency virus-1 infection: 
Developing antiretroviral drugs for treatment. Retrieved from 
http://www.fda.gov/drugs/guidancecomplianceregulatoryinformation/guidances/ucm355239.htm. 
 
2. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals 
for Human Use. (1995, November 30). ICH E3: Structure and content of clinical study reports. Retrieved 
from http://www.ich.org/products/guidelines/efficacy/article/efficacy-guidelines.html. 
 
 
 


WESTAT 
An Employee-Owned Research Corporation 
 
 
6. Proposed Summary Listings and Tables 


 
 
 
 
 
 
\\westat.com\DFS\TMB311\DA\SAP\Final\TMB-311_SAPv3_15Aug2018.doc 
 
Page 18 of 53 
ATTACHMENT 
TaiMed Biologics, Inc. 
 
Protocol TMB-311 
 
A Phase 3, Multicenter, Expanded Access Study of Ibalizumab Plus 
 an Optimized Background Regimen (OBR) in Treatment-Experienced Patients Infected With Multi-Drug Resistant (MDR) HIV-1 
 
Mock Statistical Listings 
 
November 9, 2017 
Final Version 2 
 
TaiMed Biologics, Inc 
2 Executive Circle, Suite 280 
Irvine, CA 92614 
 
 
Prepared By: 
Ken Gerald, PhD 
Director of Biostatistics 
and 
Jennifer Fulton, MS 
Biostatistician  
 
Westat 
5615 Kirby Drive, Suite 710 
Houston, TX 77005 
 
CONFIDENTIAL 


 
 
 
 
 
 
 
Notes Applicable to All Listings 
 
General Programming Notes: 
 
1. There are a few listings that might fit as they are or might have to be split once we see the output with 
actual data. 
2. All listings should start with and be sorted by Patient ID (concatenation of site number and patient 
number)and then visit date as appropriate. 
3. If columns with specific text should be widened due to the amount of text, it is up to the programmer’s 
discretion. However, please keep to the industry standard margin of 1 inch on bottom and sides and 
1.25 inches on the top. Font is Courier New 8 point. 
4. For all dates used, character format dates to capture partial dates. Use dashes where a month or day is 
missing. If entire date is missing just leave blank. i.e., – JAN2011 or 01—2011. 
5. If a programming note appears on the mock listing indicating that the footnote should appear only on the 
first page, this means the first page of output contains all footnotes and ONLY footnotes. All subsequent 
pages contain data with one footnote that says “Refer to page 1 for footnotes”. 
6. Some of the mock tables display numbers rather than x’s.  The numbers are meaningless and are for example 
only.  Where visit names are displayed in tables, these are examples as well.  Correct visit names for the 
TMB-311 study should be displayed in the actual output. 
7. Each listing should include all applicable data, even if only a subset of the full set of treatment groups 
is displayed in the mocks.  And unlike the tables and graphs, the listings should also include the 2 PI-
IND rollover patients. 
8. Sort each listing by Treatment and then Patient ID where applicable. 
 
 
 
 


TaiMed Biologics, Inc. 
TMB-311 
 
 
 
Listing 16.2.1.1 
Patient Disposition 
                                  ________________________________________________________________________________                                        
 
                                                                                           ITT         SAF       
                                                                 Patient                Population  Population   
                                         Treatment                 ID       Screened      [1]         [2]        
                                   ________________________________________________________________________________                                        
                                                                                                       
                                   C1:301/800mg             311-XX-XXX     YES           YES         YES                                                     
     
                                   C1:202/800mg             311-XX-XXX     YES           YES         YES                                                     
     
                                   C1:202/2000mg            311-XX-XXX     YES           YES         YES                                                     
     
                                   C2:800mg                    311-XX-XXX     YES           YES         YES                                                  
     
                                   ________________________________________________________________________________                                        
                                   [1]Intent-to-Treat (ITT) Population consists of all patients enrolled into the                                          
                                       study.                                                                                                              
                                   [2]Safety (SAF) Population consists of patients receiving at least one partial                                          
                                       dose of study drug.                                                                                                 
                                                                                                                                                
     
Programming note:  Add the mITT population if analyst decides it is needed later. 
Westat (Created on DDMMYYYY)                                                                                                                               
S:\TMB311\DA\SAS\L_PATDISP.SAS                                                                                                                          


TaiMed Biologics, Inc. 
TMB-311 
 
 
 
Listing 16.2.1.2 
Study Discontinuation 
 
_______________________________________________________________________________________________________________________________________________       
                                    Study        Date of    Completed          Reason for                                                              
                   Patient    Discontinuation     Last       Study             Treatment          Completed       Reason for Study         Death       
    Treatment         ID           Date        Treatment   Treatment        Discontinuation         Study          Discontinuation          Date       
 
_________________________________________________________________________________________________________________________________________________       
                                                                                                       
  C2:800mg         311-XX-XXX    20161101       20161004       NO       CONSENT WITHDRAWN OR         NO        CONSENT WITHDRAWN OR                        
                                                                        VOLUNTARY WITHDRAWAL                    VOLUNTARY WITHDRAWAL                       
     
  C2:800mg         311-XX-XXX    20160920       20160823       NO      ADVERSE EVENT-SEVERE DRUG     NO        ADVERSE EVENT-SEVERE DRUG                   
                                                                        RASH AND FEVER OF 1                     RASH AND FEVER OF 1                        
                                                                        WEEK.                                   WEEK.                                      
     
  C1:202/2000mg    311-XX-XXX    20160517       20160421       NO      INVESTIGATORS                 NO        INVESTIGATORS                               
                                                                        DECISION-INVESTIGATORS                  DECISION-LACK OF                           
                                                                        DECISION                                CLINICAL PROGRESSION                       
     
  C2:800mg         311-XX-XXX    20161101       20160810       NO      INVESTIGATORS                 NO        INVESTIGATORS                               
                                                                        DECISION-SUBJECT NEVER                  DECISION-SUBJECT NEVER                     
                                                                        CAME TO FOLOOW UP VISIT                 CAME TO F/UP VISIT                         
                                                                        BECAUSE NEVER RECOVERED                 BECAUSE NEVER RECOVERED                    
                                                                        FROM PCP                                FROM PNEUMONIA                             
     
  C1:301/800mg     311-XX-XXX    20160728       20160728       NO      CONSENT WITHDRAWN OR          NO        CONSENT WITHDRAWN OR                        
                                                                        VOLUNTARY WITHDRAWAL                    VOLUNTARY WITHDRAWAL                       
     
  C1:202/800mg     311-XX-XXX    20161004       20160720       NO      ADVERSE EVENT-SUBJECT         NO        ADVERSE EVENT-SUBJECT      20161001         
                                                                        DECEASED AS RESULT OF                   DECEASED AS RESULT OF                      
                                                                        TRAUMA DURING ACCIDENTAL                TRAUMA DURING ACCIDENTAL                   
                                                                        FALL                                    FALL                                       
     
  __________________________________________________________________________________________________________________________________________________       
Westat (Created on DDMMMYYYY)                                                                                                                               
S:\TMB311\DA\SAS\L_DISCRSN.SAS                                                                                                                          


TaiMed Biologics, Inc. 
TMB-311 
 
 
 
 
 
Listing 16.2.2.1 
Text of Inclusion and Exclusion 
 
Criterion 
Type 
Criterion 
Number 
Criterion Text 
Inclusion 
1 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
X 
 
2 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
X 
 
… 
 
 
9 
 
 
 
 
Exclusion 
1 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
X 
 
2 
 
 
… 
 
 
12 
 
 
 
 
Westat (Created on DDMMMYYYY)                                                                                                                               
S:\TMB311\DA\SAS\L_INCEXL.SAS                                                                                                                          


TaiMed Biologics, Inc. 
TMB-311 
 
 
 
 
 
Listing 16.2.2.2 
Protocol Violations 
 
 
Treatment  
Patient 
ID 
Visit 
Protocol 
Violation Code 
Details  
of Violation 
Approval 
Obtained 
Date of 
Approval 
 C1:202/800mg    311-XX-XXX 
XXXXXX 
XXX 
XXXXXXXXXXX 
Yes/No 
DDMONYYYY 
 
 C1:202/2000mg   311-XX-XXX 
XXXXXX 
XXX 
XXXXXXXXXX 
Yes/No 
DDMONYYYY 
 
 
 
 
 
 
 
 
 
 
Westat (Created on DDMMMYYYY)                                                                                                                               
S:\TMB311\DA\SAS\L_PROTVIOS.SAS                                                                                                                          


TaiMed Biologics, Inc. 
TMB-311 
 
 
 
 
 
 
Listing 16.2.2.3 
Protocol Deviations 
 
 
Treatment  
Patient 
ID 
Visit 
Protocol 
Deviation Code 
Details of  
Deviation 
Approval 
Obtained 
Date of 
Approval 
 C1:202/2000mg   311-XX-XXX 
XXXXXX 
XXX 
XXXXXXXXXXX 
Yes/No 
DDMONYYYY 
 
 C2:800mg 
311-XX-XXX 
XXXXXX 
XXX 
XXXXXXXXXX 
Yes/No 
DDMONYYYY 
 
 
 
 
 
 
 
 
 
Westat (Created on DDMMMYYYY)                                                                                                                               
S:\TMB311\DA\SAS\L_PROTDEV.SAS                                                                                                                          
 


TaiMed Biologics, Inc. 
TMB-311 
 
 
 
 
 
Listing 16.2.2.4 
Inclusion/Exclusion Criteria Violations/Deviations 
 
 
 
 
 
Treatment 
Patient 
ID 
Date of 
Informed 
Consent 
Time of 
Informed 
Consent 
(hh:mm) 
Subject be 
Enrolled in 
Study 
Criterion 
Type and 
Number [1] 
Approval 
Obtained 
 
 
Date of 
Approval 
C1:301/800mg 
311-XX-XXX 
DDMONYYYY 
XX:XX 
Yes/No 
EXC XXX/INC 
XXX 
Yes/No 
DDMONYYYY 
C1:202/800mg 
311-XX-XXX 
DDMONYYYY 
XX:XX 
Yes/No 
EXC XXX/INC 
XXX 
Yes/No 
DDMONYYYY 
            [1]Refer to Listing 16.2.2.1 for text. 
 
 
 
 
 
 
 
 
 
 
 
 
Westat (Created on DDMMMYYYY)                                                                                                                               
S:\TMB311\DA\SAS\L_INCEXLVIOS.SAS                                                                                                                          
 
 


TaiMed Biologics, Inc. 
TMB-311 
 
 
 
 
 
Listing 16.2.4.1.1 
Demographic Characteristics 
       _________________________________________________________________________________________________________________________________________           
                                                                                                           
          Treatment     Patient ID   Date of Birth   Age (years) [1]               Ethnicity                            Race                Sex            
       _________________________________________________________________________________________________________________________________________           
                                                                                                           
       C1:301/800mg      311-XX-XXX    1962-01-22           54         NOT HISPANIC OR LATINO               BLACK OR AFRICAN AMERICAN         M             
     
       C1:202/800mg      311-XX-XXX    1954-11-26           61         NOT HISPANIC OR LATINO               WHITE                             M             
     
       C2:800mg          311-XX-XXX    1988-02-11           28         NOT HISPANIC OR LATINO               BLACK OR AFRICAN AMERICAN         M             
     
       C1:2000mg         311-XX-XXX    1960-12-16           55         HISPANIC OR LATINO                   UNKNOWN                           M             
     
       C1:301/800mg      311-XX-XXX    1962-11-15           53         NOT HISPANIC OR LATINO               WHITE                             M             
     
       C2:800mg          311-XX-XXX    1966-04-21           50         NOT HISPANIC OR LATINO               WHITE                             M             
       _________________________________________________________________________________________________________________________________________           
       [1] Age = Age at Screening.                                                     
                                                                                                                                                
     
     
Westat (Created on DDMMMYYYY)                                                                                                                               
S:\TMB311\DA\SAS\L_DEMOG.SAS                                                                                                                            
 
 
 
 
 
 


TaiMed Biologics, Inc. 
TMB-311 
 
 
 
 
 
 
Listing 16.2.4.1.2 
Demographic Characteristics 
Screen Failures 
       _________________________________________________________________________________________________________________________________________           
                                                                                                           
          Treatment     Patient ID   Date of Birth   Age (years) [1]               Ethnicity                            Race                Sex            
       _________________________________________________________________________________________________________________________________________           
                                                                                                           
       SCREEN FAILURE   311-XX-XXX    1962-01-22           54         NOT HISPANIC OR LATINO               BLACK OR AFRICAN AMERICAN         M             
     
       SCREEN FAILURE   311-XX-XXX    1954-11-26           61         NOT HISPANIC OR LATINO               WHITE                             M             
     
       SCREEN FAILURE   311-XX-XXX    1988-02-11           28         NOT HISPANIC OR LATINO               BLACK OR AFRICAN AMERICAN         M             
     
       SCREEN FAILURE   311-XX-XXX    1960-12-16           55         HISPANIC OR LATINO                   UNKNOWN                           M             
     
       SCREEN FAILURE   311-XX-XXX    1962-11-15           53         NOT HISPANIC OR LATINO               WHITE                             M             
     
       SCREEN FAILURE   311-XX-XXX    1966-04-21           50         NOT HISPANIC OR LATINO               WHITE                             M             
       _________________________________________________________________________________________________________________________________________           
       [1] Age = Age at Screening.                                                     
                                                                                                                                                
     
     
Westat (Created on DDMMMYYYY)                                                                                                                               
S:\TMB311\DA\SAS\L_DEMOGSCR.SAS                
                                              


 
 
Listing 16.2.4.2 
Medical History 
 
 
Treatment 
Patient 
ID 
Medical Condition/Surgery 
Start Date 
Stop Date 
C1:301/800mg  
311-XX-XXX 
XXXXXXXXXXXXXX 
DDMONYYYY 
DDMONYYYY or ONGOING 
 
 
 
 
 
C2:800mg 
311-XX-XXX 
XXXXXXXXXXXXXX 
DDMONYYYY 
DDMONYYYY or ONGOING 
 
 
 
 
 
 
 
 
 
 
 
Westat (Created on DDMMMYYYY)                                                                                                                               
S:\TMB311\DA\SAS\L_MEDHIST.SAS                                                                                                                          
 
 
 
 
 


 
 
Listing 16.2.5.1 
Study Drug Administration 
 
 
 
 
Treatment 
Patient 
ID 
Visit 
Visit 
Date 
Dose (mg) 
Start Time 
of Infusion 
(hh:mm) 
Stop Time of 
Infusion 
(hh:mm) 
Infusion Site 
Infusion 
Side 
Starting 
Volume 
(ml) 
Ending  
Volume 
(ml) 
Was entire  
dose  
delivered? 
Reason if No or 
Interrupted 
C1:301/800m
g      
311-XX-XXX XXXXXXX 
XXXXXXX 
DDMONYYYY 
DDMONYYYY 
2000/800 
2000/800 
XX:XX 
XX:XX 
XX:XX 
XX:XX 
Cephalic Vein/Other 
Vein 
Cephalic Vein/Other 
Vein 
Left/ 
Right 
Left/ 
Right 
XXX 
 
XXX 
XXX 
 
XXX 
Yes/No/Yes w/ 
Interruption 
Yes/No/Yes w/ 
Interruption 
XXXXXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
C2:800mg 
311-XX-XXX XXXXXXX 
DDMONYYYY 
2000/800 
XX:XX 
XX:XX 
Cephalic Vein/Other 
Vein 
Left/ 
Right 
XXX 
XXX 
Yes/No/Yes w/ 
Interruption 
XXXXXXXXXX 
 
 
 
 
 
 
 
 
Westat (Created on DDMMMYYYY)                                                                                                                               
S:\TMB311\DA\SAS\L_DRUGAMIN.SAS                                                                                                                          


 
 
 
Listing 16.2.5.2 
ART Exposure 
 
 
 
Treatment 
Patient 
ID 
Medication 
Standardized 
Medication 
Name [1] 
Indication 
Start Date 
Stop Date 
Dose 
Unit 
Route 
Frequency 
C1:202/2000
mg      
311-XX-
XXX 
XXXXXXXX  
XXXXXXXX 
XXXXXXXX 
DDMONYYYY 
 
DDMONYYYY 
Or ONGOING 
XXXX 
XXXX  
XXXXX 
XX 
 
 
 
 
 
 
 
 
 
 
 
C2:800mg 
311-XX-
XXX 
XXXXXXXX  
XXXXXXXX 
XXXXXXXX 
DDMONYYYY 
DDMONYYYY 
Or ONGOING 
XXXX 
XXXX  
XXXXX 
XX 
[1]Medications were coded with WHO Drug Dictionary Version March,2014. 
 
 
 
 
 
 
 
Westat (Created on DDMMMYYYY)                                                                                                                               
S:\TMB311\DA\SAS\L_ARTEXP.SAS                                                                                                                          
 
 


 
 
Listing 16.2.5.3 
Previous and Concomitant Medications 
 
Treatment 
Patient ID 
Medication 
Standardized 
Medication 
Name [1] 
Indication 
Start Date 
Stop Date 
Dose 
Unit 
Route 
Frequency 
C1:202/800 mg 
311-XX-XXX 
XXXXXXXX  
XXXXXXXX 
XXXXXXXX 
DDMONYYYY 
 
DDMONYYYY 
Or ONGOING 
XXXX 
XXXX  
XXXXX 
XX 
 
 
 
 
 
 
 
 
 
 
 
C2:800mg 
311-XX-XXX 
XXXXXXXX  
XXXXXXXX 
XXXXXXXX 
DDMONYYYY 
DDMONYYYY 
Or ONGOING 
XXXX 
XXXX  
XXXXX 
XX 
[1]Medications were coded with WHO Drug Dictionary Version March, 2014. 
 
 
 
Westat (Created on DDMMMYYYY)                                                                                                                               
S:\TMB311\DA\SAS\L_CONMED.SAS                                                                                                                          


 
 
 
Listing 16.2.5.4 
Concomitant Procedures 
 
 
 
Treatment 
Patient 
ID 
Procedure 
Procedure Date 
Reason 
 
C1:301/800mg 
311-XX-XXX 
XXXXXXXX 
DDMONYYYY 
XXXXXXXX 
 
C2:800mg 
311-XX-XXX 
XXXXXXXX 
DDMONYYYY 
XXXXXXXX 
 
 
 
Westat (Created on DDMMMYYYY)                                                                                                                               
S:\TMB311\DA\SAS\L_CONPROCS.SAS                                                                                                                          


 
 
Listing 16.2.5.5 
Optimized Background Regimen (OBR) 
 
Treatment 
Patient 
ID 
Medication 
Standardized 
Medication 
Name [1] 
Indication Start Date 
Stop Date 
Dose 
Unit 
Route 
Frequency 
Reason 
for 
Change 
C1:301/800m
g 
311-XX-
XXX 
XXXXXXXX  
XXXXXXXX 
XXXXXXXX 
DDMONYYYY 
 
DDMONYYYY 
Or ONGOING 
XXXX 
XXXX  
XXXXX 
XX 
XXX 
 
 
 
 
 
 
 
 
 
 
 
 
C2:800mg 
311-XX-
XXX 
XXXXXXXX  
XXXXXXXX 
XXXXXXXX 
DDMONYYYY 
DDMONYYYY 
Or ONGOING 
XXXX 
XXXX  
XXXXX 
XX 
XXX 
[1]Medications were coded with WHO Drug Dictionary Version March, 2014. 
 
 
 
 
 
 
 
 
 
 
 
 
Westat (Created on DDMMMYYYY)                                                                                                                               
S:\TMB311\DA\SAS\L_OBR.SAS                                                                                                                          


 
 
Listing 16.2.5.6 
Optimized Background Regimen (OBR) Adherence 
 
Treatment 
Patient  
ID 
Visit 
Visit Date 
Has the patient taken all required 
doses of OBR 
since the last visit? 
If No Explain 
C1:202/800mg 311-XX-XXX 
XXXXX 
DDMONYYYY 
YES/NO 
XXXXXXXXXXXX 
 
 
 
 
 
 
C1:202/2000mg 311-XX-XXX 
XXXX 
DDMONYYYY 
YES/NO 
XXXXXXXXXXXX 
 
 
 
 
 
 
Westat (Created on DDMMMYYYY)                                                                                                                               
S:\TMB311\DA\SAS\L_OBRADHER.SAS                                                                                                                          


 
 
Listing 16.2.6.1 
Post-Injection Observation 
 
 
Treatment 
Patient 
ID 
Visit 
Visit Date 
Observed After 
Study Drug 
Start Time of 
Observation 
(hh:mm) 
End Time of 
Observation 
(hh:mm) 
Comments 
 C1:301/800mg 
311-XX-XXX 
XXX 
DDMONYYYY 
YES/NO 
XX:XX 
XX:XX 
XXXXXXXXXXXXXXXXX 
 
 
 
 
 
 
 
 
 
 
C2:800mg 
311-XX-XXX 
XXX 
DDMONYYYY 
YES/NO 
XX:XX 
XX:XX 
XXXXXXXXXXXXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Westat (Created on DDMMMYYYY)                                                                                                                               
S:\TMB311\DA\SAS\L_POSTINJECT.SAS                                                                                                                          
 


 
 
Listing 16.2.6.2 
CD4+ Cell Count (cells/mm^3) 
 
 
 
 
                                                                                                                                  Unimputed Original Values        Imputed with  
                                                                                                                                                                     LOCF [5]                           
 
Treatment 
Patient 
ID 
Visit 
[1] 
Visit Date 
(Study Day) 
CD4+ Cell 
Count 
(cells/mm^3) 
[2] 
CD4+ Cell Count 
Change from 
Baseline (%) 
[3] 
 
 
Toxicity 
[4] 
CD4+ Cell 
Count (cells/mm^3) 
[2] 
CD4+ Cell Count 
Change from 
Baseline (%) 
[3] 
C1:301/800mg 
311-XX-XXX 
XXXXXXX 
DDMONYYYY (XX) 
 XXX* 
XXXX 
XXXX 
 
 XXX* 
XXXX 
C2:800mg 
311-XX-XXX 
XXXXXXX 
DDMONYYYY (XX) 
XXX 
XXXX 
XXXX 
XXX 
XXXX 
 
 
 
 
 
 
 
 
 
[1] EOS=End of Study visit conducted at Week 174 (for TMB-301 rollovers)/Week 150 (for all other patients). 
[2]*=below 200 cells/mm^3 
[3]Calculated as (visit value – baseline)/baseline*100% 
[4]Toxicity is defined as 2 consecutive laboratory results, at least 14 days apart, with a CD4+ cell count below 200 
cells/mm3 that also represents a 50% reduction from the baseline CD4+ cell count. 
[5] Missing values are imputed using the Last Observation Carried Forward (LOCF) method.e 
 
 
 
 
Westat (Created on DDMMMYYYY)                                                                                                                               
S:\TMB311\DA\SAS\L_CD4.SAS                                                                                                                          
 


 
 
Listing 16.2.6.5 
Viral Load 
 
                                                                                     Unimputed Original Values             Imputed with MEF [4]            
                                                                               _____________________________________ ________________________________      
                                                                                           Chg from                              Chg from                  
                                                              Treatment Date   Viral Load  Baseline     HIV-1 RNA    Viral Load  Baseline  HIV-1 RNA       
                   Patient     Visit         Visit Date         (Study Day)      (log10     (log10       (cp/mL)       (log10     (log10    (cp/mL)        
     Treatment        ID        [2]         (Study Day)             [3]          cp/mL)     cp/mL)         [5]         cp/mL)     cp/mL)      [5]          
  ___________________________________________________________________________________________________________________________________________________      
                                                                                                                 
             
                             DAY 0      2016-08-22           2016-08-10 (159)        1.0                TND**              1.0              TND**          
 C1:301/800mg    311-XX-XXX  DAY 14                                                                                        4.9        0.0   73700          
                             WEEK 12                                                                                       4.9        0.0   73700          
                             WEEK 16                                                                                       4.9        0.0   73700          
                             WEEK 12    2016-11-14 (84)      2016-10-31 (245)        1.3       -3.6     TD**               1.3       -3.6   TD**           
                             WEEK 20                                                                                       4.9        0.0   73700          
                             WEEK 24                                                                                       4.9        0.0   73700          
                             WEEK 24    2017-02-06 (168)     2017-01-23 (329)        1.0       -3.9     TND**              1.0       -3.9   TND**          
     
                             
                  311-XX-XXX DAY 0      2016-09-07           2016-08-24 (154)        1.3                TD**               1.3              TD**           
                             DAY 14                                                                                        3.8        0.0   6530           
                             WEEK 12                                                                                       3.8        0.0   6530           
                             WEEK 16                                                                                       3.8        0.0   6530           
                             WEEK 12    2016-12-01 (352)     2016-11-17 (513)        1.0       -2.8     TND**              1.0       -2.8   TND**          
                             WEEK 20                                                                                       3.8        0.0   6530           
                             WEEK 24                                                                                       3.8        0.0   6530           
                             WEEK 24    2017-02-23 (436)     2017-02-10 (598)        1.0       -2.8     TND**              1.0       -2.8   TND**          
  ___________________________________________________________________________________________________________________________________________________      
  [1] EOS=End of Study visit conducted at Week 174 (for TMB-301 rollovers)/Week 150 (for all other patients).                                                                                                         
  [2] Visits are assigned based on study day using the windows defined in the statistical analysis plan.                                                   
  [3] Last treatment prior to viral load measurement.                                                                                                      
  [4] Viral Load results are imputed based on MEF (Missing Equals Failure). This means null viral load results are replaced with the baseline value        
      such that Change from Baseline=0 and the result is a failure. Also all records following a CONFIRMED virologic failure are set to failure.           
  [5] *=below 400 copies/mL; **=below 50 copies/mL. HIV-1 RNA level results below level of quantitation are coded as target detected (TD) or target        
      not detected (TND).                                                                                                                                  
                                                                                                                                          (Continued)      
     
     
                                                                                                                            
                                                                                                                            
 
 
 
 
 
Westat (Created on DDMMMYYYY)                                                                                                                               
S:\TMB311\DA\SAS\L_VL.SAS                                                                                                                          


 
 
Listing 16.2.6.6 
Virologic Outcome Parameters 
At EOS 
 
 
 
 
 
Treatment 
 
 
 
Patient 
ID 
 
 
 
Visit 
[1] 
 
 
 
Visit Date 
(Study Day) 
 
 
 
 Virologic 
Outcome [2] 
 
 
 
 
Virologic Failure [3] 
 
 
  
 
Virologic Success [4] 
C1:301/800mg 
311-XX-XXX 
XXXXXXX 
DDMONYYYY 
(XX) 
      XX 
XXXXXXX 
XXXXXXX 
C2:800mg 
311-XX-XXX 
XXXXXXX 
DDMONYYYY 
(XX) 
      XX 
XXXXXXX 
XXXXXXX 
 
 
 
 
 
 
 
 
[1]Visits are assigned based on study day using the windows defined in the statistical analysis plan. 
[2]Per the Snapshot Approach: 
1=Virologic success (=0.5 log copies/mL drop from Baseline in viral load) 
2a=(<0.5 log copies/mL drop from Baseline in viral load) 
2b=Discontinued because of virologic failure 
2c=Discontinued because of other reasons and drop from baseline in viral load at the time of discontinuation was <0.5 log copies/mL 
2d=OBR changed  
3a=Discontinued because of AE or death 
3b=Discontinued because of other reasons and drop from baseline in viral load at the time of discontinuation was >=0.5 log copies/mL 
3c=Missing data during the window but on study 
[3] Failure to achieve/maintain response=Patient does not have >=0.5 log10 decline from baseline(BL) by Week 12 on study drug OR 
patient has a 0.5 log10 decline from BL prior to Week 12 but fails to maintain the 0.5 log10 decline from BL with a <1 log10 increase 
from nadir on any two consecutive scheduled efficacy assessments after Week 12.  
   Rebound=Patient has a >=0.5 log10 decline from BL by Week 12 that is maintained but viral load remains >=50 copies (not suppressed), 
followed by >=1 log10 increase from nadir at two consecutive scheduled visits any time after the primary endpoint.  


 
 
   Breakthrough=Patient has suppressed viral load (< 50 copies) at any time after primary endpoint followed by >=200 copies at two 
consecutive scheduled efficacy assessments. 
[4]Suboptimal Response=Patient has a 0.5 log10 decline but does not suppress (<50 copies) at any time after primary endpoint;  
   Virologic Suppression=Patient has a 0.5 log10 decline and does suppress (<50 copies) at any time after primary endpoint 
 
 
Programming note:  See footnotes (values to the left of the =) to indicate what values will be displayed in the listing. 
 
Westat (Created on DDMMMYYYY)                                                                                                                               
S:\TMB311\DA\SAS\L_VLOUTCOMES.SAS                                                                                                                          


 
 
Listing 16.2.6.7 
Patients with Virologic Failure 
 
 
Patient 
 ID 
Visit 
Visit 
Date 
Viral Load  
(log10 copies/mL) 
Change from 
Baseline 
Treatment 
 
C1:301/800mg 
311-XX-XXX 
XXX 
DDMONYYYY 
XXX 
XXX 
 
 
 
 
 
 
C1:800 MG 
311-XX-XXX 
XXX 
DDMONYYYY 
XXX 
XXX 
Note: Virologic failure is defined as two consecutive measurements of less than a 0.5 log10 
decline from the Baseline viral load.  For the Cohort 2 and TMB-301 rollover patients, 
virologic failure will not be assessed prior to 24 weeks on study drug.  For the TMB-202 
rollover patients, virologic failure will not be assessed prior to the start of the TMB-311 
study period. 
 
 
 
 
 
Westat (Created on DDMMMYYYY)                                                                                                                               
S:\TMB311\DA\SAS\L_VLFAIL.SAS                                                                                                                          


 
 
 
Listing 16.2.7.1 
Adverse Events 
_________________________________________________________________________________________________________________________________________________________   
                             System                          Adverse                                        Sev.                   Action          Class   
            Patient          Organ           Preferred        Event       TEAE    Start Date   Stop Date   /Grade           Caus.   Taken  Outcm.    C     
Treatment      ID            Class            Term[1]        Verbatim      [2]   (Study Day)  (Study Day)    [3]     SAE     [4]     [5]     [6]    AE     
_________________________________________________________________________________________________________________________________________________________   
                                                                                                                 
C1:301/800mg  311-XX-XXX   MUSCULOSKELETAL AND  ARTHRALGIA     MILD PAIN (DUE    Y     20160923     20161010      1        N      0        0      1           
                          CONNECTIVE TISSUE                   TO FALL AT               (283)        (300)                                                    
     
C2:800mg      311-XX-XXX   NERVOUS SYSTEM       HEADACHE       WORSENING         Y     20160516     20160524      2        N      0        0      1           
                          DISORDERS                           HEADACHES                 (3)         (11)                                                     
                          INVESTIGATIONS       BREATH SOUNDS  DECREASED         Y     20160520     20160609      1        N      0        0      1           
                                               ABNORMAL       BREATH SOUNDS             (7)         (27)                                                     
C1:202/2000mg 311-XX-XXX   RENAL AND URINARY    POLLAKIURIA    URINARY           Y     20161005                   2        N      0        1      3           
                          DISORDERS                           FREQUENCY                (208)                                                                 
C1:202/800mg  311-XX-XXX   SKIN AND             RASH           MACULOPAPULAR     Y     20170119     20170214      2        N      1        1      1           
                          SUBCUTANEOUS TISSUE  MACULO-PAPU-   RASH ON                  (349)        (375)                                                    
                          DISORDERS            LAR            EXTREMITIES                                                                                    
_________________________________________________________________________________________________________________________________________________________   
[1] Adverse events are coded using MedDRA Version 17.0.                                                                                                     
[2] A treatment-emergent AE (TEAE) is defined as any event not present before exposure to study drug or any event already present that worsens in either    
   intensity or frequency following exposure to study drug. AEs with missing start dates, but with stop dates either overlapping into the dosing period    
   or missing, will be considered TEAEs                                                                                                                    
[3] Severity/Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Potentially Life Threatening, 5=Death                                                                   
[4] Causality: 0=Unrelated, 1=Possible, 2=Probable, 3=Definite                                                                                              
[5] Action Taken: 0=None, 1=Medication Given, 2=Non-Medication Therapy, 3=Suspended Study Drug, 4=Permanently Discontinued Study Drug, 99=Other             
[6] Outcome: 1=Resolved, 2=Resolved w/sequelae, 3=Ongoing, 4=Worsened, 5=Death, 7=Chronic/Stable, 98=Unknown                                                
                                                                                                                                               
     
     
Westat (Created on DDMMMYYYY)                                                                                                                               
S:\TMB311\DA\SAS\L_AE.SAS 
                                                                                                                              
 


TaiMed Biologics, Inc. 
TMB-311 
 
 
Listing 16.2.7.2 
Serious Adverse Events 
_________________________________________________________________________________________________________________________________________________________   
                             System                          Adverse                                        Sev.                   Action          Class   
            Patient          Organ           Preferred        Event       TEAE    Start Date   Stop Date   /Grade           Caus.   Taken  Outcm.    C     
Treatment      ID            Class            Term[1]        Verbatim      [2]   (Study Day)  (Study Day)    [3]     SAE     [4]     [5]     [6]    AE     
_________________________________________________________________________________________________________________________________________________________   
                                                                                                       
C2:800mg      311-XX-XXX  INVESTIGATIONS     BLOOD          LOW SERUM         Y     20161116     20161118      3        Y      0      1,99     1             
                                            POTASSIUM      POTASSIUM                (187)        (189)                                                     
                                            DECREASED                                                                                                      
     
C1:301/800mg  311-XX-XXX  INFECTIONS AND     CELLULITIS     FACE              Y     20161017     20161101      2        Y      0      1,99     7             
                         INFESTATIONS                        CELLULITIS               (153)        (168)                                                    
     
C1:202/2000mg 311-XX-XXX  NEOPLASMS BENIGN,  TONSIL CANCER  METASTATIC        Y     20161130                   4        Y      0        0      3             
                         MALIGNANT AND        METASTATIC     SQUAMOUS CELL            (190)                                                                 
                         UNSPECIFIED (INCL                   CARCINOMA OF                                                                                   
                         CYSTS AND POLYPS)                   THE RIGHT                                                                                      
                                                           TONSIL                                                                                          
C1:202/800mg  311-XX-XXX  NEOPLASMS BENIGN,  TONSIL CANCER  METASTATIC        Y     20170203     20170204      4        Y      0        1      4             
                         MALIGNANT AND        METASTATIC     SQUAMOUS CELL            (255)        (256)                                                    
                         UNSPECIFIED (INCL                   CARCINOMA OF                                                                                   
                         CYSTS AND POLYPS)                   THE RIGHT                                                                                      
                                                           TONSIL                                                                                          
                         NEOPLASMS BENIGN,  TONSIL CANCER  METASTATIC        Y     20170205     20170205      5        Y      0        1      5             
                         MALIGNANT AND        METASTATIC     SQUAMOUS CELL            (257)        (257)                                                    
                         UNSPECIFIED (INCL                   CARCINOMA OF                                                                                   
                         CYSTS AND POLYPS)                   THE RIGHT                                                                                      
_________________________________________________________________________________________________________________________________________________________   
[1] Adverse events are coded using MedDRA Version 17.0.                                                                                                     
[2] A treatment-emergent AE (TEAE) is defined as any event not present before exposure to study drug or any event already present that worsens in either    
   intensity or frequency following exposure to study drug. AEs with missing start dates, but with stop dates either overlapping into the dosing period    
   or missing, will be considered TEAEs.                                                                                                                   
[3] Severity/Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Potentially Life Threatening, 5=Death                                                                   
[4] Causality: 0=Unrelated, 1=Possible, 2=Probable, 3=Definite                                                                                              
[5] Action Taken: 0=None, 1=Medication Given, 2=Non-Medication Therapy, 3=Suspended Study Drug, 4=Permanently Discontinued Study Drug, 99=Other             
[6] Outcome: 1=Resolved, 2=Resolved w/sequelae, 3=Ongoing, 4=Worsened, 5=Death, 7=Chronic/Stable, 98=Unknown                                                
     
     
                                                                                                                                                           
     
Westat (Created on DDMMMYYYY)                                                                                                                               
 


TaiMed Biologics, Inc. 
TMB-311 
 
 
Listing 16.2.7.3 
Adverse Events Leading to Study Discontinuation or Death 
_________________________________________________________________________________________________________________________________________________________   
                             System                          Adverse                                        Sev.                   Action          Class   
            Patient          Organ           Preferred        Event       TEAE    Start Date   Stop Date   /Grade           Caus.   Taken  Outcm.    C     
Treatment      ID            Class            Term[1]        Verbatim      [2]   (Study Day)  (Study Day)    [3]     SAE     [4]     [5]     [6]    AE     
_________________________________________________________________________________________________________________________________________________________   
                                                                                                   
C1:2000mg   311-XX-XXX NEOPLASMS BENIGN,    TONSIL CANCER  METASTATIC        Y     20170205     20170205      5        Y      0        1      5             
                       MALIGNANT AND        METASTATIC     SQUAMOUS CELL            (257)        (257)                                                     
                       UNSPECIFIED (INCL                   CARCINOMA OF                                                                                    
                       CYSTS AND POLYPS)                   THE RIGHT                                                                                       
                                                           TONSIL                                                                                          
     
C1:301/800mg 311-XX-XXX GENERAL DISORDERS    PYREXIA        FEVER             Y     20160830     20160901      3        N      1       1,4     1             
                       AND ADMINISTRATION                                            (7)          (9)                                                      
                       SITE CONDITIONS                                                                                                                     
C2:800mg     311-XX-XXX INFECTIONS AND       SEPSIS         SEPSIS            Y     20160901     20161114      5        Y      0       1,4     5      YES    
                       INFESTATIONS                        SECONDARY TO             (93)         (167)                                                     
                                                           NEUTROPENIA                                                                                     
     
C1:202/800mg 311-XX-XXX INJURY, POISONING    INJURY         TRAUMA FROM       Y     20161001     20161001      5        Y      0        4      5             
                       AND PROCEDURAL                      FALL                     (157)        (157)                                                     
                       COMPLICATIONS                                                                                                                       
     
_________________________________________________________________________________________________________________________________________________________   
[1] Adverse events are coded using MedDRA Version 17.0.                                                                                                     
[2] A treatment-emergent AE (TEAE) is defined as any event not present before exposure to study drug or any event already present that worsens in either    
   intensity or frequency following exposure to study drug. AEs with missing start dates, but with stop dates either overlapping into the dosing period    
   or missing, will be considered TEAEs                                                                                                                    
[3] Severity/Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Potentially Life Threatening, 5=Death                                                                   
[4] Causality: 0=Unrelated, 1=Possible, 2=Probable, 3=Definite                                                                                              
[5] Action Taken: 0=None, 1=Medication Given, 2=Non-Medication Therapy, 3=Suspended Study Drug, 4=Permanently Discontinued Study Drug, 99=Other             
[6] Outcome: 1=Resolved, 2=Resolved w/sequelae, 3=Ongoing, 4=Worsened, 5=Death, 7=Chronic/Stable, 98=Unknown                                                
     
     
                                                                                                                                                           
     
     
                                                                                                                                                           
     
Westat (Created on DDMMMYYY)                                                                                                                               
S:\TMB311\DA\SAS\L_AEDISCDTH.SAS                                                                                                                        


TaiMed Biologics, Inc. 
TMB-311 
 
 
 
Listing 16.2.8.1.1 
Clinical Laboratory Test 
Hematology 
_____________________________________________________________________________________________________________________________________________________      
                                                                                                                     Lower     Upper    Potentially        
                Patient                  Date of Sample                                      Result                Limit of  Limit of    Clinically        
   Treatment      ID       Visit [1]      (Study Day)     Test                              (L/H)[2]       Unit     Normal    Normal   Significant[3]      
  ___________________________________________________________________________________________________________________________________________________      
                                                                                                       
  C1:301/800mg  311-XX-XXX  XXXXXXXXX   2016-03-04 (-172) Basophils                             0         10^9/L       0        0.2                        
                                                          Basophils/Total Cells                 0            %         0         2                         
                                                          Eosinophils                         0.02        10^9/L       0       0.57                        
                                                          Eosinophils/Total Cells               1            %         0        6.8                        
                                                          Hematocrit                         0.31(L)     Proport-    0.39      0.54         YES            
  C1:800mg      311-XX-XXX  XXXXXXXXX   2016-11-14 (84)   Hemoglobin                         106(L)         g/L       127       181         YES            
                                                          Leukocytes                         1.62(L)      10^9/L      3.8      10.7         YES            
                                                          Lymphocytes                        0.6(L)       10^9/L     0.91      4.28         YES            
                                                          Lymphocytes/Total Cells              37            %       15.4      48.5                        
                                                          Monocytes                           0.16        10^9/L     0.12      0.92                        
                                                          Monocytes/Total Cells                10            %        2.6      10.1                        
                                                          Neutrophils                        0.84(L)      10^9/L     1.96      7.23         YES            
                                                          Neutrophils/Total Cells              52            %       40.5       75                         
                                                          Platelets                            278        10^9/L      140       400                        
  C1:2000mg     311-XX-XXX  XXXXXXXXX    2016-11-14 (84)  Basophils                           0.08        10^9/L       0        0.2                        
                                                          Basophils/Total Cells              2.3(H)          %         0         2          YES            
                                                          Eosinophils                         0.19        10^9/L       0       0.57                        
                                                          Eosinophils/Total Cells              5.5           %         0        6.8                        
                                                          Hematocrit                          0.39       Proport-    0.39      0.54                        
  C2:800mg      311-XX-XXX  XXXXXXXXX   2016-11-14 (84)   Hemoglobin                           128          g/L       127       181                        
                                                          Leukocytes                         3.47(L)      10^9/L      3.8      10.7         YES            
                                                          Lymphocytes                         1.49        10^9/L     0.91      4.28                        
                                                          Lymphocytes/Total Cells              43            %       15.4      48.5                        
                                                          Monocytes                           0.34        10^9/L     0.12      0.92                        
                                                          Monocytes/Total Cells                9.7           %        2.6      10.1                        
                                                          Neutrophils                        1.37(L)      10^9/L     1.96      7.23         YES            
                                                          Neutrophils/Total Cells            39.5(L)         %       40.5       75          YES            
                                                          Platelets                            250        10^9/L      140       400                        
  ___________________________________________________________________________________________________________________________________________________      
  [1] For TMB301 Rollovers, BASELINE is the value recorded on Day 7 of the TMB-301 study. For TMB202 Rollovers, BASELINE is the value recorded on Day      
      0 of the TMB-202 study. Lab samples were not collected at the TMB-311 Screening for the Cohort 1 patients. EOS=End of Study visit conducted at       
      Week 96.                                                                                                                                             
  [2] L = Below lower limit of normal; H = Above upper limit of normal.                                                                                    
  [3] Potentially Clinically Significant is defined as having a result either below the lower limit of normal or above the upper limit of normal.          
     
     
Westat (Created on DDMMMYYYY)                                                                                                                               
S:\TMB311\DA\SAS\L_LABHEMA.SAS                                                                                                                          


TaiMed Biologics, Inc. 
TMB-311 
 
 
 
Listing 16.2.8.1.2 
Clinical Laboratory Test 
Chemistry 
 
 ___________________________________________________________________________________________________________________________________________________      
                                                                                                                     Lower     Upper    Potentially        
                Patient                  Date of Sample                                      Result                Limit of  Limit of    Clinically        
   Treatment      ID       Visit [1]      (Study Day)     Test                              (L/H)[2]       Unit     Normal    Normal   Significant[3]      
  ___________________________________________________________________________________________________________________________________________________      
                                                                                                       
  C1:301/800mg  311-XX-XXX  XXXXXXX   2016-03-04 (-172)  Alanine Aminotransferase             21           U/L        6        43                         
                                                         Albumin                              36           g/L       33        49                         
                                                         Alkaline Phosphatase                 100          U/L       35        131                        
                                                         Amylase                            167(H)         U/L       28        120         YES            
  C1:202/800mg  311-XX-XXX  XXXXXXX   2016-11-14 (84)    Alanine Aminotransferase             18           U/L        6        43                         
                                                         Albumin                              38           g/L       33        49                         
                                                         Alkaline Phosphatase                 131          U/L       35        131                        
                                                         Amylase                            158(H)         U/L       28        120         YES            
                                                         Aspartate Aminotransferase           20           U/L       11        36                         
  C1:202/2000mg 311-XX-XXX  XXXXXXXX   2016-03-04 (-172) Alanine Aminotransferase             21           U/L        6        43                         
                                                         Albumin                              36           g/L       33        49                         
                                                         Alkaline Phosphatase                 100          U/L       35        131                        
                                                         Amylase                            167(H)         U/L       28        120         YES            
  C2:800mg      311-XX-XXX  XXXXXXX   2016-11-14 (84)    Alanine Aminotransferase             18           U/L        6        43                         
                                                         Albumin                              38           g/L       33        49                         
                                                         Alkaline Phosphatase                 131          U/L       35        131                        
                                                         Amylase                            158(H)         U/L       28        120         YES            
                                                         Aspartate Aminotransferase           20           U/L       11        36                         
  ___________________________________________________________________________________________________________________________________________________      
  [1] For TMB301 Rollovers, BASELINE is the value recorded on Day 7 of the TMB-301 study. For TMB202 Rollovers, BASELINE is the value recorded on Day      
      0 of the TMB-202 study. Lab samples were not collected at the TMB-311 Screening for the Cohort 1 patients. EOS=End of Study visit conducted at       
      Week 96.                                                                                                                                             
  [2] L = Below lower limit of normal; H = Above upper limit of normal.                                                                                    
  [3] Potentially Clinically Significant is defined as having a result either below the lower limit of normal or above the upper limit of normal.          
                                                                                                                                           
     
     
                                                                                                                                                           
Westat (Created on DDMMMYYYY)                                                                                                                               
S:\TMB311\DA\SAS\L_LABCHEM.SAS                                                                                                                          


TaiMed Biologics, Inc. 
TMB-311 
 
 
 
 
Listing 16.2.8.1.3 
Clinical Laboratory Test 
Urinalysis 
 
               ______________________________________________________________________________________________________________________                     
                              Patient                        Date of Sample                                                                                
                 Treatment      ID            Visit           (Study Day)         Test                             Unit        Result                        
                ______________________________________________________________________________________________________________________                     
                                                                                                     
                C1:301/800mg  311-XX-XXX   XXXXXXXX          2016-03-04 (-172)  Calcium Oxalate Crystals                     Present                         
                                                                                Hyaline Casts                    /LPF           2                            
                                                                                Sediment Examination                        Positive                         
     
                                           XXXXXXXX          2016-11-14 (84)    Sediment Examination                        Positive                         
     
                                           XXXXXXXX          2017-02-06 (168)   Sediment Examination                        Positive                         
     
                C1:202/800mg  311-XX-XXX   XXXXXXXX          2016-03-16 (92)    Mucous Threads                               Present                         
     
                                           XXXXXXXX          2016-03-23 (99)    Calcium Oxalate Crystals                     Present                         
                                                                                 Sediment Examination                        Positive                        
     
                                           XXXXXXXX          2017-02-23 (436)   Amorphous Crystals                           Present                         
                                                                                 Sediment Examination                        Positive                        
     
                C2:800mg      311-XX-XXX   XXXXXXXX          2016-04-07 (-37)   Sediment Examination                        Positive                         
     
                                           XXXXXXXX          2016-05-13 (0)     Sediment Examination                        Positive                         
     
                                           XXXXXXXX          2016-05-20 (7)     Hyaline Casts                    /LPF           2                            
                                                                                 Sediment Examination                        Positive                        
     
                C1:202/2000mg  311-XX-XXX  XXXXXXXX          2016-03-11 (0)     Sediment Examination                        Negative                         
     
                                           XXXXXXXX          2016-06-03 (84)    Calcium Oxalate Crystals                     Present                         
                                                                                Mucous Threads                               Present                         
                                                                                 Sediment Examination                        Positive                        
     
                                           XXXXXXXX          2016-08-25 (167)   Sediment Examination                        Negative                         
     
                ______________________________________________________________________________________________________________________                     
                EOS=End of Study visit conducted at Week 96.                                                                                               
     
     
Westat (Created on DDMMMYYYY)                                                                                                                               
S:\TMB311\DA\SAS\L_LABURINE.SAS                                                                                                                         


TaiMed Biologics, Inc. 
TMB-311 
 
 
 
Listing 16.2.8.1.4 
Abnormal Laboratory Results 
________________________________________________________________________________________________________________________________________________________    
                                                                                                                        Lower    Upper    Potentially      
             Patient                  Date of Sample                                            Result                 Limit of Limit of   Clinically      
Treatment      ID        Visit [1]     (Study Day)       Category           Test               (L/H)[2]        Unit     Normal   Normal  Significant[3]    
________________________________________________________________________________________________________________________________________________________    
                                                                                                         
C1:301/800mg   311-XX-XXXX  XXXXXXXXX    2016-03-04 (-172) CHEMISTRY       Amylase                167(H)         U/L       28      120         YES          
                                                                       Direct Bilirubin          1(L)         umol/L      2        7          YES          
                                                          HEMATOLOGY      Hematocrit             0.31(L)     Proportion   0.39     0.54       YES          
                                                                                                               of 1                                        
                                                                       Hemoglobin               106(L)         g/L       127      181         YES          
                                                                       Leukocytes               1.62(L)       10^9/L     3.8      10.7        YES          
                                                                       Lymphocytes              0.6(L)        10^9/L     0.91     4.28        YES          
                                                                       Neutrophils              0.84(L)       10^9/L     1.96     7.23        YES          
C1:202/800mg   311-XX-XXX   XXXXXXXXX    2016-11-14 (84)   CHEMISTRY       Amylase               158(H)         U/L        28      120         YES          
                                                                       Bilirubin                1.5(L)        umol/L      3        21         YES          
                                                                       Direct Bilirubin         1(L)         umol/L       2        7          YES          
                                                          HEMATOLOGY      Basophils/Total       2.3(H)          %         0        2          YES          
                                                                       Cells                                                                              
                                                                       Leukocytes               3.47(L)       10^9/L     3.8      10.7        YES          
                                                                       Neutrophils              1.37(L)       10^9/L     1.96     7.23        YES          
                                                                       Neutrophils/Total        39.5(L)         %        40.5      75         YES          
                                                                       Cells                                                                              
C1:202/2000mg  311-XX-XXX   XXXXXXXXX    2017-02-06 (168)  CHEMISTRY       Amylase                133(H)         U/L       28      120         YES          
                                                                       Direct Bilirubin          1(L)         umol/L      2        7          YES          
                                                          HEMATOLOGY      Hematocrit             0.37(L)     Proportion   0.39     0.54       YES          
                                                                                                               of 1                                        
                                                                       Hemoglobin               124(L)         g/L       127      181         YES          
     
C2:800mg       311-XX-XXX   XXXXXXXXX    2016-03-23 (99)   CHEMISTRY       Alanine                68(H)         U/L        6        43         YES          
                                                                       Aminotransferase                                                                   
                                                                       Aspartate                 59(H)         U/L        11       36         YES          
                                                                       Aminotransferase                                                                   
                                                                       Cholesterol              3.03(L)       mmol/L     4.53     7.71        YES          
                                                                       Creatine Kinase          393(H)         U/L        39      308         YES          
________________________________________________________________________________________________________________________________________________________    
[1] For TMB301 Rollovers, BASELINE is the value recorded on Day 7 of the TMB-301 study. For TMB202 Rollovers, BASELINE is the value recorded on Day 0 of    
   the TMB-202 study. Lab samples were not collected at the TMB-311 Screening for the Cohort 1 patients. EOS=End of Study visit conducted at Week 96.      
[2] L = Below lower limit of normal; H = Above upper limit of normal.                                                                                       
[3] Potentially Clinically Significant is defined as having a result either below the lower limit of normal or above the upper limit of normal.             
     
     
Westat (Created on DDMMMYYYY)       
S:\TMB311\DA\SAS\L_LABABN.SAS         
                                                                                                                        
   


TaiMed Biologics, Inc. 
TMB-311 
 
 
 
Listing 16.2.8.1.5 
Other Laboratory Results 
 
                                                                                                                             
                                                                                                                        Lower    Upper      Potentially      
              Patient                  Date of Sample                                            Result                 Limit of Limit of   Clinically      
Treatment        ID       Visit [1]     (Study Day)         Category           Test              (L/H)[2]       Unit     Normal   Normal    Significant[3]    
________________________________________________________________________________________________________________________________________________________    
                                                                                                         
C1:301/800mg    311-XX-XXXX  XXXXXXXXX    2016-03-04 (-172)   CHEMISTRY     Amylase                  167(H)         U/L        28      120         YES        
                                                                        Direct Bilirubin          1(L)         umol/L      2        7          YES          
                                                          HEMATOLOGY    Hematocrit               0.31(L)     Proportion   0.39     0.54        YES          
                                                                                                               of 1                                        
                                                                        Hemoglobin               106(L)         g/L       127      181         YES          
                                                                        Leukocytes               1.62(L)       10^9/L     3.8      10.7        YES          
                                                                        Lymphocytes              0.6(L)        10^9/L     0.91     4.28        YES          
                                                                        Neutrophils              0.84(L)       10^9/L     1.96     7.23        YES          
C1:202/800mg    311-XX-XXX   XXXXXXXXX    2016-11-14 (84)     CHEMISTRY     Amylase                  158(H)         U/L        28      120         YES        
                                                                        Bilirubin                1.5(L)        umol/L      3        21         YES          
                                                                        Direct Bilirubin          1(L)         umol/L      2        7          YES          
C1:202/2000mg   311-XX-XXX   XXXXXXXXX    2017-02-06 (168)    CHEMISTRY     Amylase                  133(H)         U/L        28      120         YES        
                                                                        Direct Bilirubin          1(L)         umol/L      2        7          YES          
                                                          HEMATOLOGY    Hematocrit               0.37(L)     Proportion   0.39     0.54        YES          
                                                                                                               of 1                                        
________________________________________________________________________________________________________________________________________________________    
[1] For TMB301 Rollovers, BASELINE is the value recorded on Day 7 of the TMB-301 study. For TMB202 Rollovers, BASELINE is the value recorded on Day 0 of    
   the TMB-202 study. Lab samples were not collected at the TMB-311 Screening for the Cohort 1 patients. EOS=End of Study visit conducted at Week 96.      
[2] L = Below lower limit of normal; H = Above upper limit of normal.                                                                                       
[3] Potentially Clinically Significant is defined as having a result either below the lower limit of normal or above the upper limit of normal.             
     
Westat (Created on DDMMYYYY) 
S:\TMB311\DA\SAS\L_LABOTH.SAS    
 


TaiMed Biologics, Inc. 
TMB-311 
 
 
 
 
Listing 16.2.8.2 
Viral Resistance Testing 
 
                                                                                                                                    Entry Inhibitors      
                                                                                                                                       (Resistance)        
                                                                                                                                  ______________________   
                                                                Reverse                                                                            Enfu-   
            Patient                 Visit                    Transcriptase              Protease         Integrase Genese  Trop-   Ibal-   Mara-   virt-   
Treatment       ID        Visit       Date     Test Type       (Resistance)            (Resistance)         (Resistance)     ism   izumab  viroc    ide     
_________________________________________________________________________________________________________________________________________________________   
                                                                                                         
C1:301/800mg    311-xx-xxx  SCREENING  2015-09-08  Geno   Abacavir (Y)            Atazanavir (ATV) (N)    Dolutegravir (Y)   DM      Y       Y       Y      
                                                         Stavudine (P)           Tipranavir (P)                                                            
                                                         Tenofovir (Y)                                                                                     
                                                         Zidovudine (P)                                                                                    
                                                         Delavirdine (N)         Atazanavir (ATV/r) (P)  Elvitegravir (Y)                                  
                                                         Didanosine (Y)          Darunavir (Y)           Raltegravir (Y)                                   
                                                         Efavirenz (N)           Fosamprenavir (P)                                                         
     
                                              Pheno      Abacavir (Y)            Atazanavir (ATV) (Y)    Dolutegravir (Y)                                  
                                                         Stavudine (Y)           Tipranavir (Y)                                                            
                                                         Tenofovir (Y)                                                                                     
                                                         Zidovudine (Y)                                                                                    
                                                         Delavirdine (N)         Atazanavir (ATV/r) (Y)  Elvitegravir (Y)                                  
                                                         Didanosine (Y)          Darunavir (Y)           Raltegravir (Y)                                   
                                                         Efavirenz (N)           Fosamprenavir (Y)                                                         
     
                       WEEK 9     2015-11-03  Geno       Abacavir (P)            Atazanavir (ATV) (N)    Dolutegravir (Y)   DM      N       Y       Y      
                                                         Stavudine (N)           Tipranavir (P)                                                            
_________________________________________________________________________________________________________________________________________________________   
[1] EOS=End of Study visit conducted at Week 96.                                                                                                            
[2] Note:  Abbreviations for Resistance:  Y = Sensitive, P = Partially Sensitive, N = Resistant                                                             
                                                                                                                                             (Continued)   
   
  
     
Westat (Created on DDMMMYYYY)                                                                                                                               
S:\TMB301\DA\SAS\L_VRTEST.SAS                                                                                                                           
 


TaiMed Biologics, Inc. 
TMB-311 
 
 
 
 
 
Listing 16.2.8.3 
Vital Signs 
 
                                                                        Height   Weight   Temp.    Rate    Resp. Rate   Systolic Blood  Diastolic Blood    
            Patient                 Visit       Scheduled      Time      (cm)     (kg)     (C)    (bpm)   (breaths/min) Pressure(mmHg)  Pressure(mmHg)     
Treatment      ID        Visit       Date      Time Point     (hh:mm)    [2]      [2]      [2]     [2]         [2]            [2]             [2]          
________________________________________________________________________________________________________________________________________________________    
                                                                                                         
C1:301/800mg 311-XX-XXX   SCREENING  2015-08-04                             170       69     36.5     62         16             129             85            
     
                         DAY 0      2015-08-31                                       69     36.9     81         16             108             68            
     
                         DAY 7      2015-09-08  PRE-INFUSION     10:45                      36.9     74         15             127             76            
                                    2015-09-08  POST-INFUSION    12:00                      36.8     76         16             110             69            
     
                         DAY 21     2015-09-22  PRE-INFUSION     10:00                      36.9     82         15             103             68            
                                    2015-09-22  POST-INFUSION    11:05                      36.8     80         15             115             72            
     
                         WEEK 5     2015-10-06  PRE-INFUSION     10:40                      36.4*    67         16             126             83            
                                    2015-10-06  POST-INFUSION    11:40                      36.8     76         15             122             72            
     
                         WEEK 7     2015-10-19  PRE-INFUSION     11:20                      38.9*    117*       15             123             72            
                                    2015-10-19  POST-INFUSION    12:15                      37.1     108        15             124             72            
     
                         WEEK 19    2016-01-14  PRE-INFUSION     12:45                      36.8     79         16             108             65            
                                    2016-01-14  POST-INFUSION    13:25                      36.7     78         16             109             70            
     
C1:202/800mg  311-XX-XXX  SCREENING  2015-08-05                             179       83     36.6     69         15             124             85            
     
________________________________________________________________________________________________________________________________________________________    
[1]EOS=End of Study visit conducted at Week 96.                                                                                                             
[2]*Denotes Potentially Clinically Significant Vital Signs outside of these ranges: Temperature: 36.44-37.22 C; Pulse: 60-110 BPM; Respiration rate:        
   12-20 breaths per minute; Blood Pressure: Systolic 100-140 mmHg; Diastolic 60-90 mmHg                                                                   
                                                                                                                                             
     
Westat (Created on DDMMMYYYY) 
S:\TMB301\DA\SAS\L_VITALS.SAS  
     


TaiMed Biologics, Inc. 
TMB-311 
 
 
 
 
                                                                                                                              
Listing 16.2.8.4 
Physical Examinations 
 
 
 
Treatment 
Patient 
ID 
Visit 
Visit Date 
Performed 
at Visit 
Body System [1] 
Status (Details) 
 
C1:301/800mg   
311-XX-XXX 
Screening 
DDMONYYYY 
Yes/No 
HEENT 
Cardiovascular 
Musculoskeletal 
Lymphatic 
Respiratory 
Gastrointestinal 
Skin 
Neurological 
Additional PE Findings 
Normal/Abnormal/Not Done 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 


TaiMed Biologics, Inc. 
TMB-311 
 
 
 
 
C1:202/800mg   
311-XX-XXX 
Day 0 
DDMONYYYY 
Yes/No 
Cardiovascular 
Lymphatic 
Respiratory 
Abdomen 
Extremities 
Neurological 
Additional PE Findings 
Normal/Abnormal/Not Done 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
[1]A complete physical examination is performed only at <list correct visits>. An abbreviated physical examination is performed at 
other visits. 
 
 
 
 
 
 
 
 
Westat (Created on DDMMYYYY) 
S:\TMB311\DA\SAS\L_PHYSEXAM.SAS    
 


TaiMed Biologics, Inc. 
TMB-311 
 
 
 
 
Listing 16.2.9 
Extent of Treatment Exposure 
                                             
                             ___________________________________________________________________________________________                                  
                                                      Patient         Start Date of          Last Date of       Years on                                   
                              Treatment                 ID              Ibalizumab           Ibalizumab*       Ibalizumab                                  
                              ___________________________________________________________________________________________                                  
                                                                                                         
                              C1:301/800mg             311-XX-XXX         04MAR2016             21FEB2017         1.0                                     
     
                              C1:202/800mg             311-XX-XXX         23MAR2016             23FEB2017         0.9                                     
     
                              C1:202/2000mg            311-XX-XXX         16JUN2015             10FEB2017         1.7                                     
     
                              C2:800mg                 311-XX-XXX         19AUG2015             15FEB2017          1.5                                     
     
     
                              ___________________________________________________________________________________________                                  
                              *Last Dose recorded prior to the Data Cutoff Date.                                                                           
                                                                                                               
   
  
Westat (Created on DDMMMYYYY)                                                                                                                               
S:\TMB311\DA\SAS\L_TRTEXP.SAS