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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00183261




Registration number
NCT00183261
Ethics application status
Date submitted
13/09/2005
Date registered
16/09/2005
Date last updated
11/06/2013

Titles & IDs
Public title
Immune Response to a Therapeutic HIV Vaccine Followed by Treatment Interruption in Patients With Acute or Recent HIV Infection
Scientific title
A Randomized Phase II Study of Therapeutic Immunization and Treatment Interruption Among Subjects Who Began Potent Antiretroviral Therapy Within 30 Days of Diagnosis of Acute or Recent HIV Infection
Secondary ID [1] 0 0
10025
Secondary ID [2] 0 0
AIN504/A5218
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV Infections 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Sexually transmitted infections
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - MRKAd5 HIV-1 gag/pol/nef
Other interventions - MRKAd5 HIV-1 gag/pol/nef placebo

Experimental: 1 - Participants will receive the MRKAd5 HIV-1 gag/pol/nef vaccine at study entry and on Weeks 4 and 26

Placebo Comparator: 2 - Participants will receive the MRKAd5 HIV-1 gag/pol/nef vaccine placebo at study entry and on Weeks 4 and 26


Other interventions: MRKAd5 HIV-1 gag/pol/nef
1.5 x 1010 Ad vg/mL, 1.0 mL administered intramuscularly

Other interventions: MRKAd5 HIV-1 gag/pol/nef placebo
1.0 mL administered intramuscularly

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Average of log10 HIV-1 RNA viral load
Timepoint [1] 0 0
At Weeks 58 and 63
Primary outcome [2] 0 0
Frequency of Grade 3 or 4 systemic adverse events, the occurrence of a severe or life-threatening injection site adverse event, or death
Timepoint [2] 0 0
Throughout study
Secondary outcome [1] 0 0
Distribution of plasma HIV RNA viral load
Timepoint [1] 0 0
At Weeks 63 and 87
Secondary outcome [2] 0 0
Proportion of patients with controlled viremia and their respective distribution of plasma HIV RNA viral load
Timepoint [2] 0 0
At Weeks 63 and 87
Secondary outcome [3] 0 0
Mean viral burden, defined as time-averaged area under the log10 HIV-1 RNA viral load curve
Timepoint [3] 0 0
At Weeks 63 and 87
Secondary outcome [4] 0 0
HIV DNA levels
Timepoint [4] 0 0
At Weeks 30, 38, 63, and 87
Secondary outcome [5] 0 0
HIV-1 DNA levels
Timepoint [5] 0 0
At Weeks 30, 38, 46, 50, 63, and 87
Secondary outcome [6] 0 0
Magnitude and absolute change in CD4 and CD8 counts
Timepoint [6] 0 0
At Weeks 63 and 87
Secondary outcome [7] 0 0
Percent and absolute change in the number of HIV-1- specific CD8 cells, as measured by interferon (IFN)-gamma Elispot assay and intracellular cytokine staining
Timepoint [7] 0 0
Through Week 30
Secondary outcome [8] 0 0
Percent and absolute change in the cytokine secretion patterns and the proliferative capacity of HIV-1- specific CD4 and CD8 cells, as measured by multiparameter flow cytometry
Timepoint [8] 0 0
Through Week 30
Secondary outcome [9] 0 0
Breadth and magnitude of HIV-1- specific CD4 and CD8 cell responses
Timepoint [9] 0 0
Throughout study
Secondary outcome [10] 0 0
Time to reach the specified virologic or immunologic criteria for reinitiating antiretroviral therapy after treatment interruption
Timepoint [10] 0 0
Throughout study
Secondary outcome [11] 0 0
Frequency of Grade 3 or 4 systemic adverse events or the occurrence of a severe or life-threatening injection site adverse event, or HIV-related events, AIDS-defining infections, and death from time of vaccination
Timepoint [11] 0 0
Throughout study
Secondary outcome [12] 0 0
Cell-associated infectivity in latently infected cells
Timepoint [12] 0 0
At Week 63
Secondary outcome [13] 0 0
Cell-associated infectivity at Week 63 and immunologic responses
Timepoint [13] 0 0
At Weeks 63 and 87

Eligibility
Key inclusion criteria
- Initiated HAART within 30 days of an acute or recent HIV-1 infection diagnosis. More
information on this criterion can be found in the protocol.

- Initiated HAART within 30 days of documented acute or recent HIV-1 infection without
interruption for more than 7 days

- Sustained viral suppression, defined as a viral load of 500 copies/mL or less 12
months prior to baseline with an undetectable HIV-1 RNA viral load between 60 to 7
days prior to baseline

- CD4 count of 450 cells/mm3 or more OR 35% or more between 60 to 14 days prior to
baseline

- Ad5 neutralizing antibody titer of 200 or less at screening

- Willing to follow all study procedures and schedules

- Willing to interrupt HAART for at least 24 weeks following completion of the
vaccination stage

- Negative for hepatitis B surface antigen (HBsAg) at screening

- Willing to use acceptable forms of contraception

- Infected with HIV-1 subtype B, if this information is available
Minimum age
18 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Virologic relapse, defined as 2 consecutive measurements of viral load of 500
copies/mL or more at least 7 days apart within 12 months of baseline visit

- Received more than 7 days of continuous HAART other than that received within 16 days
of acute or recent HIV-1 infection. Participants who received HAART as part of
post-exposure prophylaxis (PEP) more than 6 months prior to the start of initial HAART
may be eligible, provided that they did not acquire HIV-1 infection from the event
that required PEP.

- History of anaphylaxis or allergy to vaccine components, including Tris buffer,
magnesium chloride, and polysorbate 80 (Tween)

- History of clinically significant heart, lung, kidney, liver, pancreatic,
gastrointestinal, or neurological disease that, in the opinion of the study
investigator, may interfere with the study

- Contraindication to intramuscular (IM) injection, such as anticoagulant therapy or
thrombocytopenia

- Receipt of any immune globulin or blood products within 3 months prior to baseline

- Receipt of any live vaccine within 30 days prior to baseline or any inactivated
vaccine within 14 days prior to baseline

- Previous receipt of any HIV vaccine. Participants that were documented to have
received only placebo are not excluded.

- History of any AIDS-defining illness. If a participant's sole AIDS-defining illness is
Kaposi's sarcoma limited to the skin and is not anticipated to require systemic
chemotherapy, that participant is not excluded.

- Currently receiving drugs or biologics not approved by the Food and Drug
Administration (FDA) other than investigational HIV medications

- Current or past participation in other studies that might alter the participant's
response to the study vaccination

- Use of any immunomodulatory agents, including but not limited to interleukin-2 (IL-2),
granulocyte/macrophage-colony stimulating factor (GM-CSF), and systemic
corticosteroids, within 30 days prior to baseline

- Active alcohol or substance use that, in the investigator's opinion, may interfere
with the study

- Any other criteria or condition that, in the investigator's opinion, may interfere
with the study

- Unwilling or unable to contribute to the planned peripheral blood mononuclear cell
(PBMC) blood collection

- Pregnancy or breastfeeding

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Holdsworth House Medical Practice CRS - Darlinghurst
Recruitment hospital [2] 0 0
St. Vincent's Hospital CRS - Darlinghurst
Recruitment hospital [3] 0 0
Taylor Square Private Clinic CRS - Darlinghurst
Recruitment hospital [4] 0 0
AIDS Research Initiative, Darlinghurst CRS - Darlinghurst
Recruitment hospital [5] 0 0
407 Doctors (Australia) AIEDRP - Sydney
Recruitment hospital [6] 0 0
AIDS Research Initiative (Australia) AIEDRP - Sydney
Recruitment hospital [7] 0 0
St. Vincent's Hosp. (Australia) AIEDRP - Sydney
Recruitment hospital [8] 0 0
Taylor Square Private Clinic (Australia) AIEDRP - Sydney
Recruitment hospital [9] 0 0
Holdsworth House Gen. Practice (Australia) AIEDRP - Sydney
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
- Darlinghurst
Recruitment postcode(s) [3] 0 0
2010 - Sydney
Recruitment postcode(s) [4] 0 0
- Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Missouri
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Rhode Island
Country [8] 0 0
American Samoa
State/province [8] 0 0
Surry Hills

Funding & Sponsors
Primary sponsor type
Government body
Name
National Institute of Allergy and Infectious Diseases (NIAID)
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Acute Infection and Early Disease Research Program
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
AIDS Clinical Trials Group
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to determine whether the HIV vaccine MRKAd5 HIV-1 gag/pol/nef
followed by treatment interruption can increase immune system function in adults with acute
or recent HIV infection who have started taking anti-HIV drugs.
Trial website
https://clinicaltrials.gov/show/NCT00183261
Trial related presentations / publications
Markowitz M, Jin X, Hurley A, Simon V, Ramratnam B, Louie M, Deschenes GR, Ramanathan M Jr, Barsoum S, Vanderhoeven J, He T, Chung C, Murray J, Perelson AS, Zhang L, Ho DD. Discontinuation of antiretroviral therapy commenced early during the course of human immunodeficiency virus type 1 infection, with or without adjunctive vaccination. J Infect Dis. 2002 Sep 1;186(5):634-43. Epub 2002 Aug 9.
Moss RB, Brandt C, Giermakowska WK, Savary JR, Theofan G, Zanetti M, Carlo DJ, Wallace MR. HIV-specific immunity during structured antiviral drug treatment interruption. Vaccine. 2003 Mar 7;21(11-12):1066-71.
Papasavvas E, Ortiz GM, Gross R, Sun J, Moore EC, Heymann JJ, Moonis M, Sandberg JK, Drohan LA, Gallagher B, Shull J, Nixon DF, Kostman JR, Montaner LJ. Enhancement of human immunodeficiency virus type 1-specific CD4 and CD8 T cell responses in chronically infected persons after temporary treatment interruption. J Infect Dis. 2000 Sep;182(3):766-75. Epub 2000 Aug 17.
Rosenberg ES, Altfeld M, Poon SH, Phillips MN, Wilkes BM, Eldridge RL, Robbins GK, D'Aquila RT, Goulder PJ, Walker BD. Immune control of HIV-1 after early treatment of acute infection. Nature. 2000 Sep 28;407(6803):523-6.
Public notes

Contacts
Principal investigator
Name 0 0
Susan Little, MD
Address 0 0
University of California, San Diego AIDS Vaccine Research Center
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications