Safety, Tolerability and Immune Response to LC002, an Experimental Therapeutic Vaccine, in Adults Receiving HAART

This study has been completed.
Sponsor:
Collaborator:
AIDS Clinical Trials Group
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00270205
First received: December 21, 2005
Last updated: March 5, 2014
Last verified: March 2014
Results First Received: September 7, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator);   Primary Purpose: Treatment
Condition: HIV Infections
Interventions: Biological: LC002 standard vaccination
Biological: LC002 high-dose vaccination
Biological: LC002 placebo vaccination

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were enrolled from February 2006 to October 2008 in 5 different U.S. sites. Enrollment was done by cohort with each cohort enrolling six participants for LC002 vaccine and 2 participants for its corresponding placebo. Cohorts were enrolled sequentially, with later cohorts receiving higher dose of the LC002 vaccine.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Study participants were HIV-1-infected men and women 18-50 years of age with CD4 count >350 cells/mm^3 and plasma HIV-1 RNA <50 copies/ml (on an ultrasensitive assay) and who were on a stable HAART regimen. One enrolled participant never started study treatment/vaccination.

Reporting Groups
  Description
A: 0.1 mg DNA/Participant Vaccination at Weeks 1, 7, 13 Participants receiving three separate low-dose vaccinations of LC002 (0.1 mg DNA/participant, 0.8 ml total, administered over two skin sites [on the left and right upper back] of 80 cm^2 each, 0.4 ml/site) at weeks 1, 7, and 13.
C: 0.4 mg DNA/Participant Vaccination at Weeks 1, 7, 13 Participants receiving three separate high-dose vaccinations of LC002 (0.4 mg DNA/participant, 3.2 ml total, administered over four skin sites [on the left and right upper back and left and right upper ventral thigh] of 80 cm^2 each, 0.8 ml/site) at weeks 1, 7, and 13.
E: 0.4 mg DNA/Participant Vaccination at Weeks 0,1,6,7,12,13 Participants receiving six separate high-dose vaccinations of LC002 (0.4 mg DNA/participant, 3.2 ml total, administered over four skin sites [on the left and right upper back and left and right upper ventral thigh] of 80 cm^2 each, 0.8 ml/site) at study entry and weeks 1, 6, 7, 12, and 13.
Placebo All participants receiving vaccinations of LC002 placebo were combined together in this arm/group. This includes those participants in arms B, D and F.

Participant Flow:   Overall Study
    A: 0.1 mg DNA/Participant Vaccination at Weeks 1, 7, 13     C: 0.4 mg DNA/Participant Vaccination at Weeks 1, 7, 13     E: 0.4 mg DNA/Participant Vaccination at Weeks 0,1,6,7,12,13     Placebo  
STARTED     6     6 [1]   6     7  
COMPLETED     5     6     6     6  
NOT COMPLETED     1     0     0     1  
Lost to Follow-up                 1                 0                 0                 1  
[1] 7 participants enrolled. One never started study vaccination and was excluded from all analyses.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
A: 0.1 mg DNA/Participant Vaccination at Weeks 1, 7, 13 Participants receiving three separate low-dose vaccinations of LC002 (0.1 mg DNA/participant, 0.8 ml total, administered over two skin sites [on the left and right upper back] of 80 cm^2 each, 0.4 ml/site) at weeks 1, 7, and 13.
C: 0.4 mg DNA/Participant Vaccination at Weeks 1, 7, 13 Participants receiving three separate high-dose vaccinations of LC002 (0.4 mg DNA/participant, 3.2 ml total, administered over four skin sites [on the left and right upper back and left and right upper ventral thigh] of 80 cm^2 each, 0.8 ml/site) at weeks 1, 7, and 13.
E: 0.4 mg DNA/Participant Vaccination at Weeks 0,1,6,7,12,13 Participants receiving six separate high-dose vaccinations of LC002 (0.4 mg DNA/participant, 3.2 ml total, administered over four skin sites [on the left and right upper back and left and right upper ventral thigh] of 80 cm^2 each, 0.8 ml/site) at study entry and weeks 1, 6, 7, 12, and 13.
Placebo All participants receiving vaccinations of LC002 placebo were combined together in this arm/group. This includes those participants in arms B, D and F.
Total Total of all reporting groups

Baseline Measures
    A: 0.1 mg DNA/Participant Vaccination at Weeks 1, 7, 13     C: 0.4 mg DNA/Participant Vaccination at Weeks 1, 7, 13     E: 0.4 mg DNA/Participant Vaccination at Weeks 0,1,6,7,12,13     Placebo     Total  
Number of Participants  
[units: participants]
  6     6     6     7     25  
Age [1]
[units: years]
Median ( Inter-Quartile Range )
  44  
  ( 32 to 48 )  
  41  
  ( 38 to 43 )  
  46  
  ( 34 to 47 )  
  34  
  ( 30 to 35 )  
  39  
  ( 32 to 45 )  
Age, Customized [1]
[units: participants]
         
18-30     1     1     1     2     5  
31-40     2     2     1     5     10  
41-50     3     3     4     0     10  
Gender [2]
[units: participants]
         
Female     1     0     0     1     2  
Male     5     6     6     6     23  
Region of Enrollment  
[units: participants]
         
United States     6     6     6     7     25  
[1] Age (in years) at study entry. Participants who never started study vaccination were excluded.
[2] Participants who never started study vaccination were excluded.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percent of Participants With Primary Safety Endpoint   [ Time Frame: From start of study vaccination to 28 days after the last study vaccination ]

2.  Secondary:   Time-averaged Area Under the Curve (AUC) of CD4+ T-cell Count in PBMCs   [ Time Frame: From start of study vaccination to week 61 ]

3.  Secondary:   Time-averaged AUC of CD8+ T-cell Count in PBMCs   [ Time Frame: From start of study vaccination to week 61 ]

4.  Secondary:   Time-averaged AUC of the Magnitude of HIV-specific Immune Response, as Determined by Taking the Mean of the Number of Spot-forming Cells/10^6 PBMCs Observed in Each PHPC Assay for IFN-gamma Production for Gag p17, Gag p24, Gag p15 and Tat/Rev.   [ Time Frame: From start of study vaccination to week 37 ]

5.  Secondary:   Time-averaged AUC of the Magnitude of HIV-specific Immune Response, as Determined by the Number of Spot-forming Cells/10^6 PBMCs Observed in Each PHPC Assay for IFN-gamma Production for Gag p17, Gag p24, Gag p15 and Tat/Rev.   [ Time Frame: From start of study vaccination to week 37 ]

6.  Secondary:   Time-averaged AUC of the Magnitude of HIV-specific Immune Response, as Determined by Taking the Mean of the Number of Spot-forming Cells/10^6 PBMCs Observed in Each ELISPOT Assay for IFN-gamma Production for Gag p17, Gag p24, Gag p15 and Tat/Rev.   [ Time Frame: From start of study vaccination to week 37 ]

7.  Secondary:   Time-averaged AUC of the Magnitude of HIV-specific Immune Response, as Determined by the Number of Spot-forming Cells/10^6 PBMCs Observed in Each ELISPOT Assay for IFN-gamma Production for Gag p17, Gag p24, Gag p15 and Tat/Rev.   [ Time Frame: From start of study vaccination to week 37 ]

8.  Secondary:   Anti-dsDNA Antibody Response   [ Time Frame: From start of study vaccination to week 61 ]

9.  Secondary:   Time-averaged AUC of T-cell Count of HIV-1-specific CD4+ T-cell Subsets, Based on Flow Cytometry With CFSE Staining to Detect Antigen-specific Lymphocyte Proliferation Responding to p24 Protein, Gag/Pol/Env and Tat/Rev   [ Time Frame: From start of study vaccination to week 24 ]

10.  Secondary:   Time-averaged AUC of T-cell Count of HIV-1-specific CD4+ T-cell Subsets, Based on Flow Cytometry With CFSE Staining to Detect Antigen-specific Lymphocyte Proliferation Responding to Whole HIV-1 Antigen   [ Time Frame: From start of study vaccination to week 24 ]

11.  Secondary:   Time-averaged AUC of T-cell Count of HIV-1-specific CD4+ T-cell Subsets, Based on Flow Cytometry With CFSE Staining to Detect Antigen-specific Lymphocyte Proliferation Responding to Anti-CD3   [ Time Frame: From start of study vaccination to week 24 ]

12.  Secondary:   Time-averaged AUC of T-cell Percent of HIV-1-specific CD4+ T-cell Subsets, Based on Flow Cytometry With CFSE Staining to Detect Antigen-specific Lymphocyte Proliferation Responding to p24 Protein, Gag/Pol/Env and Tat/Rev.   [ Time Frame: From start of study vaccination to week 24 ]

13.  Secondary:   Time-averaged AUC of T-cell Percent of HIV-1-specific CD4+ T-cell Subsets, Based on Flow Cytometry With CFSE Staining to Detect Antigen-specific Lymphocyte Proliferation Responding to Whole HIV-1 Antigen   [ Time Frame: From start of study vaccination to week 24 ]

14.  Secondary:   Time-averaged AUC of T-cell Percent of HIV-1-specific CD4+ T-cell Subsets, Based on Flow Cytometry With CFSE Staining to Detect Antigen-specific Lymphocyte Proliferation Responding to Anti-CD3   [ Time Frame: From start of study vaccination to week 24 ]

15.  Secondary:   Time-averaged AUC of T-cell Count of HIV-1-specific CD8+ T-cell Subsets, Based on Flow Cytometry With CFSE Staining to Detect Antigen-specific Lymphocyte Proliferation Responding to p24 Protein, Gag/Pol/Env, Tat/Rev and Whole HIV-1 Antigen.   [ Time Frame: From start of study vaccination to week 24 ]

16.  Secondary:   Time-averaged AUC of T-cell Count of HIV-1-specific CD8+ T-cell Subsets, Based on Flow Cytometry With CFSE Staining to Detect Antigen-specific Lymphocyte Proliferation Responding to Anti-CD3   [ Time Frame: From start of study vaccination to week 24 ]

17.  Secondary:   Time-averaged AUC of T-cell Percent of HIV-1-specific CD8+ T-cell Subsets, Based on Flow Cytometry With CFSE Staining to Detect Antigen-specific Lymphocyte Proliferation Responding to p24 Protein, Gag/Pol/Env, Tat/Rev and Whole HIV-1 Antigen.   [ Time Frame: From start of study vaccination to week 24 ]

18.  Secondary:   Time-averaged AUC of T-cell Percent of HIV-1-specific CD8+ T-cell Subsets, Based on Flow Cytometry With CFSE Staining to Detect Antigen-specific Lymphocyte Proliferation Responding to Anti-CD3   [ Time Frame: From start of study vaccination to week 24 ]

19.  Secondary:   Time-averaged AUC of T-cell Count of HIV-1-specific CD4+ T-cell Subsets, Based on Flow Cytometry to Detect Antigen-specific IFN-gamma-producing Cells Responding to Whole Zn-finger Inactivated Virus Stimulation and Various HIV-1 Peptide Antigens   [ Time Frame: From start of study vaccination to week 24 ]

20.  Secondary:   Time-averaged AUC of T-cell Percent of HIV-1-specific CD4+ T-cell Subsets, Based on Flow Cytometry to Detect Antigen-specific IFN-gamma-producing Cells Responding to Whole Zn-finger Inactivated Virus Stimulation and Various HIV-1 Peptide Antigens   [ Time Frame: From start of study vaccination to week 24 ]

21.  Secondary:   Time-averaged AUC of T-cell Count of HIV-1-specific CD8+ T-cell Subsets, Based on Flow Cytometry to Detect Antigen-specific IFN-gamma-producing Cells Responding to Whole Zn-finger Inactivated Virus Stimulation and Various HIV-1 Peptide Antigens   [ Time Frame: From start of study vaccination to week 24 ]

22.  Secondary:   Time-averaged AUC of T-cell Percent of HIV-1-specific CD8+ T-cell Subsets, Based on Flow Cytometry to Detect Antigen-specific IFN-gamma-producing Cells Responding to Whole Zn-finger Inactivated Virus Stimulation and Various HIV-1 Peptide Antigens   [ Time Frame: From start of study vaccination to week 24 ]

23.  Secondary:   Time-averaged AUC of T-cell Count of HIV-1-specific CD4+ T-cell Subsets, Based on Flow Cytometry to Detect Antigen-specific IL-2-producing Cells Responding to Whole Zn-finger Inactivated Virus Stimulation and Various HIV-1 Peptide Antigens   [ Time Frame: From start of study vaccination to week 24 ]

24.  Secondary:   Time-averaged AUC of T-cell Percent of HIV-1-specific CD4+ T-cell Subsets, Based on Flow Cytometry to Detect Antigen-specific IL-2-producing Cells Responding to Whole Zn-finger Inactivated Virus Stimulation and Various HIV-1 Peptide Antigens   [ Time Frame: From start of study vaccination to week 24 ]

25.  Secondary:   Time-averaged AUC of T-cell Count of HIV-1-specific CD8+ T-cell Subsets, Based on Flow Cytometry to Detect Antigen-specific IL-2-producing Cells Responding to Whole Zn-finger Inactivated Virus Stimulation and Various HIV-1 Peptide Antigens   [ Time Frame: From start of study vaccination to week 24 ]

26.  Secondary:   Time-averaged AUC of T-cell Percent of HIV-1-specific CD8+ T-cell Subsets, Based on Flow Cytometry to Detect Antigen-specific IL-2-producing Cells Responding to Whole Zn-finger Inactivated Virus Stimulation and Various HIV-1 Peptide Antigens   [ Time Frame: From start of study vaccination to week 24 ]

27.  Secondary:   Lymphocyte Proliferation Stimulation Index (SI) in Response to Whole HIV-1 Antigen, p24 Antigen, and Pooled HIV-1 Peptide Antigens   [ Time Frame: Throughout study ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

28.  Secondary:   Breadth of HIV-1-specific Immune Response, as Determined by the Number of Overlapping HIV-1 Peptides for Which the ELISPOT Assay for IFN-gamma Production is Observed to Have Five or More Spot-forming Cells/ 10^5 PBMCs   [ Time Frame: Throughout study ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
This is a Phase I/II small sample study that was not powered for the secondary efficacy endpoints.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Clinicaltrials.gov Coordinator
Organization: Center for Biostatistics in AIDS Research, Harvard School of Public Health
phone: (617)432-2829
e-mail: CBAR.ClinicalTrials.Gov@sdac.harvard.edu


Publications:
Somogyi E, Xu J, Gudics A, Toth J, Kovacs AL, Lori F, Lisziewicz J. A plasmid DNA immunogen expressing fifteen protein antigens and complex virus-like particles (VLP+) mimicking naturally occurring HIV. Vaccine 29: 744-753, 2011.
Lorincz O, Toke ER, Somogyi E, Horkay F, Chandran P, Douglas JF, Szebeni J, Lisziewicz J. Structure and biological activity of pathogen-like synthetic nanomedicines. Nanomedicine: Nanotechnology, Biology, and Medicine. In press.
Gudmundsdotter L, Wahren B, Haller BK, Boberg A, Edback U, Bernasconi D, Butto S, Gaines H, Imami N, Gotch F, Lori F, Lisziewicz J, Sandstrom E, Hejdeman B. Amplified antigen-specific immune responses in HIV-1 infected individuals in a double blind DNA immunization and therapy interruption trial. Vaccine 29(33):5558-5566, 2011.


Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00270205     History of Changes
Other Study ID Numbers: A5176, 10126, ACTG A5176
Study First Received: December 21, 2005
Results First Received: September 7, 2011
Last Updated: March 5, 2014
Health Authority: United States: Food and Drug Administration