Therapeutic Intensification Plus Immunomodulation to Decrease the HIV-1 Viral Reservoir (EraMune02)

Tracking Information
First Submitted Date ICMJE	September 9, 2009
First Posted Date ICMJE	September 14, 2009
Results First Submitted Date	September 4, 2014
Results First Posted Date	September 12, 2014
Last Update Posted Date	September 12, 2014
Study Start Date ICMJE	November 2009
Actual Primary Completion Date	July 2013 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: September 10, 2014)	Change From Baseline in HIV DNA in PBMCs at Week 56 [ Time Frame: 56 weeks ]
Original Primary Outcome Measures ICMJE; (submitted: September 11, 2009)	HIV proviral DNA [ Time Frame: 56 weeks ]
Change History	Complete list of historical versions of study NCT00976404 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: September 10, 2014)	Change From Baseline in HIV DNA in Rectal Tissue at Week 56 [ Time Frame: Week 56 ]; Change From Baseline in CD4+ T Cell Count at Week 56 [ Time Frame: Week 56 ]; HIV Specific T-cell Response to Env [ Time Frame: 36 weeks ]HIV-specific immunity: Interferon gamma ELISpot response to Env (clades A) at week 36 (one month after rAd5 boosting); Serious Adverse Events Attributed to Study Treatments [ Time Frame: 56 weeks ]Grade 3 or 4 serious adverse events related to study treatments (raltegravir, maraviroc, or HIV-recombinant Ad5-based vaccine)
Original Secondary Outcome Measures ICMJE; (submitted: September 11, 2009)	HIV DNA in gut lymphoid tissue [ Time Frame: 56 weeks ]; HIV plasma viral load (RNA) [ Time Frame: 56 weeks ]; CD4+ T cell count [ Time Frame: 56 weeks ]; HIV-specific immunity [ Time Frame: 56 weeks ]; T cell activation (CD38) [ Time Frame: 56 weeks ]; Adenovirus-specific immunity [ Time Frame: 56 weeks ]; Adverse events attributed to study treatments (raltegravir, maraviroc, or HIV-recombinant Ad5-based vaccine) [ Time Frame: 56 weeks ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Therapeutic Intensification Plus Immunomodulation to Decrease the HIV-1 Viral Reservoir
Official Title ICMJE	Multicenter, Randomized, Non-comparative, Controlled Study of Therapeutic Intensification Plus Immunomodulation in HIV-infected Patients With Long-term Viral Suppression
Brief Summary	The objective of this study is to discover a new approach in which human immunodeficiency virus (HIV) can be eradicated from an infected individual by intensified antiretroviral treatment coupled with immunomodulation. The hypothesis is that eradication is possible only if very potent antiretroviral drugs are delivered in conjunction with an immunomodulatory agent that simultaneously attack the viral reservoirs.
Detailed Description	The objective of this study is to measure the impact of immunomodulation plus treatment intensification on the HIV reservoir in HIV-infected patients who have viral suppression on combination antiretroviral therapy. Treatment regimens first will be intensified by the addition of raltegravir and maraviroc for 8 week followed by immunomodulation with the NIH HIV-rAd5 vaccine plus DNA prime-boost for 24 weeks. The primary endpoint is measurement of change in peripheral cellular HIV DNA. A decrease of 0.5 log is considered significant. A secondary endpoints include change in HIV DNA in the rectal mucosa, immunologic changes in the peripheral blood and safety.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	HIV Infection
Intervention ICMJE	Biological: DNA + HIV-rAd5 vaccine 4 mg subcutaneous injection at weeks 8 (DNA prime), 12 (DNA prime), 16 (DNA prime), and 32 (HIV-rAd5); Drug: ART intensification (raltegravir) raltegravir 400 mg PO BID for 56 weeks Other Name: Isentress; Drug: ART intensification (maraviroc) maraviroc 150, 300, or 600 mg PO BID (depending on PK interactions with other medications) for 56 weeks Other Names: Selzentry Celsentri
Study Arms	Active Comparator: Maraviroc + raltegravir intensification ART Intensification (addition of raltegravir and maraviroc to suppressive ART for 56 weeks) Interventions: Drug: ART intensification (raltegravir) Drug: ART intensification (maraviroc); Experimental: Maraviroc + raltegravir intens. plus DNA + HIV-rAd5 vaccine ART Intensification (addition of raltegravir and maraviroc for 56 weeks) PLUS immunomodulation therapy with DNA prime vaccine (Weeks 8,12,16) + HIV-recombinant Ad5-based vaccine (Week 32) Interventions: Biological: DNA + HIV-rAd5 vaccine Drug: ART intensification (raltegravir) Drug: ART intensification (maraviroc)
Publications *	Achenbach CJ, Assoumou L, Deeks SG, Wilkin TJ, Berzins B, Casazza JP, Lambert-Niclot S, Koup RA, Costagliola D, Calvez V, Katlama C, Autran B, Murphy RL; EraMune 02 study team. Effect of therapeutic intensification followed by HIV DNA prime and rAd5 boost vaccination on HIV-specific immunity and HIV reservoir (EraMune 02): a multicentre randomised clinical trial. Lancet HIV. 2015 Mar;2(3):e82-91. doi: 10.1016/S2352-3018(15)00026-0. Epub 2015 Feb 17.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: September 11, 2009)	28
Original Estimated Enrollment ICMJE	Same as current
Actual Study Completion Date	June 2014
Actual Primary Completion Date	July 2013 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: HIV-1 infection; At least 3 years of ART without interruption (less than one month cumulative); ART regimen unchanged in the 3 months prior to screening; One HIV plasma viral load (RNA) documented at least 3 years prior to entry, and at least 2 HIV plasma viral load (RNA) documented per year thereafter; HIV plasma viral load (RNA) ≤ 500 copies/mL at least 3 years prior to entry, and HIV plasma viral load < 500 copies/mL for >90% of the measures thereafter; HIV plasma viral load (RNA) below the limit of detection for all values within the past year (one virologic blip allowed); HIV plasma viral load below the limit of detection within 60 days of entry; CD4+ count ≥ 350 cells/mm3 within 60 days of entry; Proviral DNA ≥10 and ≤1000 copies/106 PBMCs within 75 days of entry; Adeno5 neutralizing antibody titers of 250 or less within 75 days of entry; Hemoglobin ≥ 10 g/dL within 60 days of entry; Platelets ≥ 100,000 per microliter within 60 days of entry; Hepatic transaminases (ALT and AST) ≤ 2.5 x ULN within 60 days of entry; Creatinine clearance > 50 mL/min by the Cockcroft-Gault equation within 60 days of entry Exclusion Criteria: Sexually active men and women who will not practice at least one form of barrier birth control (male partner using condoms, female partner using condoms, other barrier contraception, etc); Pregnancy; Inability or unwillingness to provide informed consent; HBsAg positive; HCV antibody positive or HCV RNA detectable; Previous use of an integrase inhibitor (ie raltegravir) or a CCR5 inhibitor (ie maraviroc, vicriviroc). Use of raltegravir for non-treatment failure indications such as intensification or toxicity switches is allowed.; Immunologic therapeutic intervention (e.g. IL-2) within the past year; Participation in another clinical drug or device trial where the last dose of drug was within the past 30 days or an investigational medical device is currently implanted; Diagnosis of cancer within the last 5 years (except basal cell cutaneous cancers and cutaneous KS not requiring systemic therapy); Co-morbid condition with an expected survival of less than 12 months; History of hypersensitivity to vaccination; History of autoimmune disease, such as systemic lupus erythematosis (SLE) or Hashimoto's thyroiditis; Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 70 Years (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00976404
Other Study ID Numbers ICMJE	EraMune02
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Robert L. Murphy, Northwestern University
Study Sponsor ICMJE	Robert L. Murphy
Collaborators ICMJE	Objectif Recherche Vaccins SIDA; National Institute of Allergy and Infectious Diseases (NIAID); Pfizer; Merck Sharp & Dohme Corp.
Investigators ICMJE	Study Chair: Robert Murphy, MD Northwestern University
PRS Account	Northwestern University
Verification Date	September 2014
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP