HIV-1-Gag Conserved-Element DNA Vaccine (p24CE) as Therapeutic Vaccination in HIV-Infected Persons With Viral Suppression on Antiretroviral Therapy
Phase: PHASE1
Conditions: HIV Infections
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

 
 
 
A5369 Version 1.0, LOA #2 (04/16/19) 
IND Number: 018257 
 
 
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ACTG NETWORK COORDINATING CENTER 
Social & Scientific Systems 
8757 Georgia Avenue, 12th Floor 
Silver Spring, MD  20910-3714 
Phone: (301) 628-3000 
Fax: (301) 628-3302 
 
 
LETTER OF AMENDMENT 
 
DATE:  
April 16, 2019 
 
TO: 
ACTG CTU Principal Investigators, CRS Leaders, and CTU/CRS Coordinators at 
A5369 Protocol-Specific Sites 
 
FROM: 
A5369 Protocol Team  
 
SUBJECT: 
Letter of Amendment #2 for Protocol A5369, Version 1.0, 03/09/18, entitled “HIV-1-Gag 
Conserved-Element DNA Vaccine (p24CE) as Therapeutic Vaccination in HIV-Infected 
Persons with Viral Suppression on Antiretroviral Therapy” 
 
 
The following information affects the A5369 study and must be forwarded to your institutional 
review board (IRB)/ethics committee (EC) as soon as possible for their information and review. 
This Letter of Amendment (LOA) must be approved by your IRB/EC before implementation.  
 
The following information may also affect the Sample Informed Consent. Your IRB/EC is 
responsible for determining the process of informing participants of the contents of this LOA. 
 
Upon receiving final IRB/EC and any other applicable regulatory entity approvals for this LOA, 
sites should implement the LOA immediately. Sites are still required to submit an LOA 
registration packet to the Division of AIDS (DAIDS) Protocol Registration Office (PRO) at the 
Regulatory Support Center. Sites will receive a registration notification for the LOA once the 
DAIDS PRO verifies that all required LOA registration documents have been received and are 
complete. An LOA registration notification from the DAIDS PRO is not required prior to 
implementing the LOA. A copy of the LOA registration notification, along with this letter and 
any IRB/EC correspondence, should be retained in the site’s regulatory file. 
 
This LOA is being implemented for the following reasons: 
 
• 
To revise the requirement for leukapheresis evaluation; to update other sections and the 
sample informed consent accordingly.  
• 
To revise the plasma HIV-1 RNA inclusion criterion. 
• 
To clarify the preferred method and options for urinalysis testing. 
• 
To remove the Immunology Quality Assurance (IQA) requirement for CD4/CD8 T cell testing. 
• 
To allow for additional pre-leukapheresis testing as needed.  
 
 

 
 
 
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IND Number: 018257 
 
 
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1. Section 3.0, STUDY DESIGN, is revised as shown below. The protocol is limiting 
enrollment to three participants per site until 60 days after the last participating site is 
activated. Noting the importance of leukapheresis evaluation for this study, the 
protocol is updated to note that the first three participants enrolled at each site are 
required to have leukapheresis at pre-entry and at week 26 until at least 60 days 
after the last participating site is activated and at least 50% of the target accrual has 
agreed to the leukaphereses.  
 
A5369 is a phase I/IIa, randomized, double-blinded, placebo-controlled study in 
which 40 study participants will be randomized 2:1:1 to the p24CE/full-length 
gagDNA vaccine arm versus full-length gagDNA vaccine arm versus placebo 
arm. HIV-specific immunologic assays will be done at baseline and after the last 
dose of vaccine. Cells and plasma will also be obtained after the second prime 
vaccine dose, processed, and stored. Immunologic assays may be performed at 
this timepoint depending on the results of the assays done at baseline and after 
the last dose of vaccine. HIV-1 reservoir assays will be done at baseline and 
after the last dose of vaccine. Enrollment slots for participants agreeing to have 
leukaphereses will be reserved for a minimum of 20 participants. These 
participants are required to have leukapheresis at both the pre-entry and week 
26 visit. Until 60 days after the last participating site is activated, each site 
will be limited to three participants in screening/enrollment at any given 
time. During this time period, these first three participants at each site will 
be required to agree at the screening visit to undergo the leukaphereses at 
the pre-entry and week 26 timepoints. Once the 60 day period after the last 
participating site is activated has passed, and at least 50% of the target 
accrual has agreed to undergo the leukaphereses, a study participant 
agreeing to the leukaphereses will be optional but highly recommended. 
The study team will inform the participating sites when this 
leukapheresis-optional period has begun. 
 
2. Section 4.1.5 is revised as shown below. This revision is to allow sites to enroll 
participants who meet other eligibility criteria except for the HIV-1 RNA value 
unavailable for one of the two windows mentioned below.  
 
4.1.5 One documented plasma HIV-1 RNA that is below the limit of detection of an 
FDA-approved assay between 24 and 36 months prior to the screening HIV-1 
RNA and/or one documented plasma HIV-1 RNA that is below the limit of 
detection of an FDA-approved assay between 12 and 24 months prior to the 
screening HIV-1 RNA, and one documented HIV-1 RNA that is below the limit of 
detection of an FDA-approved assay collected fewer than 12 months prior to the 
screening HIV-1 RNA (see section 4.1.6).  
 
NOTE: A single, unconfirmed plasma HIV-1 RNA above the limit of detection but <400 
copies/mL is allowed if followed by an HIV-1 RNA below detectable limits, but not 
in the 6 months prior to screening. 
 
NOTE: One documented plasma HIV-1 RNA that is below the limit of detection 
between 24 and 36 months prior to the screening HIV-1 RNA and one 

 
 
 
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between 12 and 24 months prior to the screening HIV-1 RNA are preferred. 
However, in cases where a plasma HIV-1 RNA is not available in one of 
these windows, but there has been uninterrupted ART during the window 
and suppressed HIV-1 RNA before and after the window, the participant 
may be enrolled.  
 
3. Section 4.1.16 is revised as shown below. 
 
4.1.16 Indication of willingness to have the leukapheresis procedure. 
 
NOTE: Until 60 days after the last participating site is activated, each site 
will be limited to three participants in screening/enrollment at any given 
time. During this time period, these first three participants at each site will 
be required to agree at the screening visit to undergo the leukaphereses at 
the pre-entry and week 26 timepoints. Once the 60 day period after the last 
participating site is activated has passed, and at least 50% of the target 
accrual has agreed to undergo the leukaphereses, a study participant 
agreeing to the leukaphereses will be optional but highly recommended. 
The study team will inform the participating sites when this leukapheresis-
optional period has begun. Leukapheresis will be required if the study has 
reached 50% of the accrual target and less than 20 participants have agreed to 
have the leukapheresis procedure. 
 
4. Section 4.2.5, updated via LOA #1, is revised to make a wording error correction as shown 
below. 
 
4.2.5 A skin-fold measurement of the cutaneous and subcutaneous tissue for 
eligible injection sites (on the medial deltoid or vastus lateralis muscles) 
that does not exceeds 50 mm. 
 
 
 

 
 
 
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5. Section 6.1, Schedule of Evaluations, is updated as shown below. 
 
Evaluation 
Screening 
Pre-Entry 
Entry 
(Week 0) 
Post-Entry Evaluations 
(Weeks) 
Premature 
Treatment/Study 
Discontinuation 
Evaluations 
Post 
Vaccination #1 
4 
Deferred Week 
4 (See section 
6.3.10) 
Post 
Vaccination #2 
6 
12 
Deferred Week 
12 
(See section 
6.3.10) 
Post 
Vaccination #3 
24 
Deferred Week 
24 
(See section 
6.3.10) 
Post 
Vaccination #4 
26 
48 
Leukapheresis 
(Optional see 
section 6.3.14) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 

 
 
 
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6. Under section 6.3.7, Laboratory Evaluations, Urinalysis is revised as shown below. 
 
Urinalysis 
Dipstick only alone is acceptable; other methodologies are also acceptable. 
Sites may perform a laboratory urinalysis if needed to meet site-specific 
requirements. 
 
7. Under section 6.3.8, Immunologic Studies, CD4/CD8 is revised as shown below. 
 
CD4/CD8 
Obtain absolute CD4/CD8 T cell count and percentages within 60 days prior to 
entry from a laboratory that possesses a CLIA certification or equivalent. 
 
For entry and post-entry evaluations, all laboratories must possess a CLIA 
certification or its equivalent and must be certified for protocol testing by the 
DAIDS Immunology Quality Assurance (IQA) Program. 
 
8. Section 6.3.14, Leukapheresis (Optional), is revised as below. In addition, a NOTE is added 
to this section. 
 
6.3.14 Leukapheresis (Optional) 
 
Leukapheresis will be performed at pre-entry and week 26. Until 60 days after 
the last participating site is activated, each site will be limited to three 
participants in screening/enrollment at any given time. During this time 
period, these first three participants at each site will be required to agree at 
the screening visit to undergo the leukaphereses at the pre-entry and week 
26 timepoints. Once the 60 day period after the last participating site is 
activated has passed, and at least 50% of the target accrual has agreed to 
undergo the leukaphereses, a study participant agreeing to the 
leukaphereses will be optional but highly recommended. The study team 
will inform the participating sites when this leukapheresis-optional period 
has begun. Enrollment slots for participants agreeing to have leukapheresis will 
be reserved for a minimum of 20 participants. Participants agreeing to have 
leukapheresis performed at pre-entry are also required to have leukapheresis 
performed at week 26. 
 
NOTE: Sites may perform additional pre-leukapheresis testing (e.g., 
PT/INR) to meet site-specific requirements. 
 
9. Several sections in APPENDIX I, SAMPLE INFORMED CONSENT, are revised as shown 
below. 
 
Screening 
If you decide to take part in this research study, you will be asked to sign this 
consent form. You will come to the clinic to have a screening visit. Tests will be 
done at the screening visit to see if it is safe for you to join the study. The 
screening visit will take about 1 hour, but it may be shorter or longer. Prior to 

 
 
 
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screening or at Screening visit, the site staff will inform you whether 
leukapheresis is required. 
 
Pre-Entry 
If you qualify for the study, you will return to the clinic about 2 weeks after your 
screening visit for a Pre-Entry visit. The visit is expected to last between 3 to 4 
hours 
 
At the pre-entry visit: 
• 
You will have a total of about 3 tablespoons of blood drawn from a vein in 
your arm. 
• 
You will have blood collected and stored for future immunologic testing (to 
measure the body’s ability to fight infection).  
• 
You will have a pregnancy test done, if you are a woman able to become 
pregnant. 
• 
You will have blood collected to measure CD4/CD8 T cell counts (the number 
of white blood cells that fight infection). 
• 
You will have blood collected for human leukocyte antigen (HLA) typing and 
testing. 
• 
You will have blood stored for future tests.  
• 
If you agree are one of the first 3 participants to be enrolled at your site 
you may be required to have leukapheresis performed (your site can tell you 
if you will be required to have leukapheresis). You will also be required to 
have a leukapheresis performed at the week 26 visit. By collecting blood 
using this procedure, researchers are able to get many more white blood 
cells than is usually possible. If you are not required to have 
leukapheresis, this procedure is optional but highly recommended. 
• 
If you agree, you will have stool samples collected to study the different kind 
of bacteria in your stool. These samples will be stored and will be tested after 
the study is over. You will not be given the results. (This test is optional) 
 
10. Protocol Signature Page 
 
Per a regulatory requirement by the DAIDS, a Protocol Signature Page (PSP) is appended 
for submission to the DAIDS Protocol Registration System (DPRS) as part of the LOA 
registration packet. 
 

 
 
 
A5369 Version 1.0, LOA #2 (04/16/19) 
IND Number: 018257 
 
 
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HIV-1-Gag Conserved-Element DNA Vaccine (p24CE) as Therapeutic Vaccination in 
HIV-Infected Persons with Viral Suppression on Antiretroviral Therapy 
 
SIGNATURE PAGE 
 
 
I will conduct the study in accordance with the provisions of this protocol and all applicable 
protocol-related documents. I agree to conduct this study in compliance with United States (US) 
Health and Human Service regulations (45 CFR 46); applicable US Food and Drug 
Administration regulations; standards of the International Conference on Harmonization 
Guideline for Good Clinical Practice (E6); Institutional Review Board/Ethics Committee 
determinations; all applicable in-country, state, and local laws and regulations; and other 
applicable requirements (e.g., US National Institutes of Health, Division of AIDS) and 
institutional policies. 
 
 
 
 
 
Principal Investigator: _____________________________________________________ 
 
Print/Type 
 
 
 
 
 
Signed: _______________________________________________Date: _____________ 
 
Name/Title