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

HIV Infection Clinical Trial

— EraMune02  

Official title:

Multicenter, Randomized, Non-comparative, Controlled Study of Therapeutic Intensification Plus Immunomodulation in HIV-infected Patients With Long-term Viral Suppression

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00976404
• Other study ID #: EraMune02
• Status: Completed
• Phase: Phase 2
• First received: September 9, 2009
• Last updated: September 10, 2014
• Start date: November 2009
• Est. completion date: June 2014

Study information

• Verified date: September 2014
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: June 2014
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infection

Intervention

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
• ART intensification (maraviroc)
maraviroc 150, 300, or 600 mg PO BID (depending on PK interactions with other medications) for 56 weeks

Locations

Country	Name	City	State
United States	Northwestern University	Chicago	Illinois
United States	Cornell University	New York	New York
United States	University of California San Francisco	San Francisco	California

Sponsors (5)

Lead Sponsor	Collaborator
Robert L. Murphy	Merck Sharp & Dohme Corp., National Institute of Allergy and Infectious Diseases (NIAID), Objectif Recherche Vaccins SIDA, Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in HIV DNA in PBMCs at Week 56		56 weeks	No
Secondary	Change From Baseline in HIV DNA in Rectal Tissue at Week 56		Week 56	No
Secondary	Change From Baseline in CD4+ T Cell Count at Week 56		Week 56	No
Secondary	HIV Specific T-cell Response to Env	HIV-specific immunity: Interferon gamma ELISpot response to Env (clades A) at week 36 (one month after rAd5 boosting)	36 weeks	No
Secondary	Serious Adverse Events Attributed to Study Treatments	Grade 3 or 4 serious adverse events related to study treatments (raltegravir, maraviroc, or HIV-recombinant Ad5-based vaccine)	56 weeks	Yes