Clinical trial NCT00107549: Safety of Recombinant HIV Vaccines in HIV Infected Young Adults on Stable Therapy
Official title: A Phase I, Open-Label Study to Evaluate the Safety and Tolerability of Recombinant HIV-1 Vaccines in HIV-1 Infected Young Adults With Control of HIV-1 Replication and on Stable Highly Active Antiretroviral Therapy (HAART)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: Treatment Experienced
HIV Therapeutic Vaccine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2005-04-06
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 24
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the safety of two recombinant HIV vaccines in HIV infected young adults on stable anti-HIV therapy.

Detailed description: By helping to control viral replication, HAART has dramatically improved the prognosis for HIV infected individuals. However, because of extensive side effects, some of which may be acute and life-threatening, many patients find it difficult to tolerate a HAART regimen. HAART-associated long-term morbidity or mortality contribute to this difficulty. Administering an HIV therapeutic vaccine might allow HIV infected individuals to delay or interrupt treatment, avoiding the side effects associated with antiretroviral exposure. This study will evaluate the safety of two injections of two recombinant therapeutic vaccines in HIV infected young adults who are currently on stable HAART.

This study will last 72 weeks. All participants will receive two rMVA vaccines (env/gag and tat/rev/nef-RT) at study entry and at Week 4 and two rFPV vaccines (env/gag and tat/rev/nef-RT) at Weeks 8 and 24. Safety will be assessed immediately after each immunization and at 1 hour and 48 hours postimmunization. There will be 16 study visits over 72 weeks. A physical exam, blood collection, and administration of an adherence module will occur at most visits. An electrocardiogram (ECG) will occur at study entry and Weeks 2 and 10. Urine collection will occur at study entry and Weeks 4, 8, and 24.

Eligibility criteria: Inclusion Criteria:

* HIV-1 infected
* CD4 count of 350 cells/mm3 or greater
* If hepatitis B or C infected, infection must be chronic and stable
* Normal electrocardiogram (ECG)
* On stable HAART consisting of at least 3 different antiretrovirals from 2 different classes AND with a viral load of less than 100 copies/ml for at least 6 months prior to study entry
* Willing to use acceptable forms of contraception. Females enrolled in the study must use contraception for at least 21 days prior to first vaccination until the last study visit. Males enrolled in the study must use a condom from the first vaccination until one month after the last vaccination.
* Willing to follow all study requirements
* Available for follow-up for the duration of the study

Exclusion Criteria:

* History of allergic reaction to eggs or egg products
* Known hypersensitivity to vaccine components
* Chemotherapy for active cancer in the 12 months prior to study entry
* Prior vaccination with any HIV-1 vaccine
* Prior vaccination against smallpox
* Prior vaccinia immunization
* Any immunization within 1 month of study screening
* History of or known active heart disease including myocardial infarction, angina pectoris, congestive heart failure, cardiomyopathy, pericarditis, stroke or transient ischemic attack, chest pain or shortness of breath with activity such as walking upstairs, mitral valve prolapse, or other heart conditions under a doctor's care
* Immunomodulatory agents, gamma globulin, or investigational agents within 6 months of study entry
* Systemic steroids, including nonprescription street steroids, within 6 months of study entry
* Documented or suspected serious bacterial infection, metabolic illness, cancer, or immediate life-threatening condition
* Any clinically significant diseases other than HIV infection or clinically significant findings during study screening that, in the investigator's opinion, may interfere with the study
* Current alcohol or drug abuse that, in the investigator's opinion, may interfere with the study
* Pregnancy or breastfeeding

Primary outcomes:
measure: Development of any adverse events of Grade 3 or higher
timeFrame: Throughout study
measure: Development of adverse events of Grade 3 or higher attributed to the study vaccines
timeFrame: Throughout study
measure: Viral breakthrough to greater than 1,000 copies/ml
timeFrame: During the first 24 weeks of study
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles NICHD CRS
state: California
city: Los Angeles
country: United States
facility: Usc La Nichd Crs
state: California
city: Aurora
country: United States
facility: Univ. of Colorado Denver NICHD CRS
state: Colorado
city: Chicago
country: United States
facility: Chicago Children's CRS
state: Illinois
city: Baltimore
country: United States
facility: Univ. of Maryland Baltimore NICHD CRS
state: Maryland
city: New York
country: United States
facility: Columbia IMPAACT CRS
state: New York
city: Durham
country: United States
facility: DUMC Ped. CRS
state: North Carolina
city: Memphis
country: United States
facility: St. Jude/UTHSC CRS
state: Tennessee
city: San Juan
country: Puerto Rico
facility: Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS
Study officials:
affiliation: Pediatric Infectious Diseases, Duke University
name: Coleen K. Cunningham, MD
role: STUDY_CHAIR
References:
citation: Caputo A, Gavioli R, Ensoli B. Recent advances in the development of HIV-1 Tat-based vaccines. Curr HIV Res. 2004 Oct;2(4):357-76. doi: 10.2174/1570162043350986.
citation: Cosma A, Nagaraj R, Buhler S, Hinkula J, Busch DH, Sutter G, Goebel FD, Erfle V. Therapeutic vaccination with MVA-HIV-1 nef elicits Nef-specific T-helper cell responses in chronically HIV-1 infected individuals. Vaccine. 2003 Dec 8;22(1):21-9. doi: 10.1016/s0264-410x(03)00538-3.
citation: Kent SJ, Zhao A, Best SJ, Chandler JD, Boyle DB, Ramshaw IA. Enhanced T-cell immunogenicity and protective efficacy of a human immunodeficiency virus type 1 vaccine regimen consisting of consecutive priming with DNA and boosting with recombinant fowlpox virus. J Virol. 1998 Dec;72(12):10180-8. doi: 10.1128/JVI.72.12.10180-10188.1998.
citation: Mwau M, Cebere I, Sutton J, Chikoti P, Winstone N, Wee EG, Beattie T, Chen YH, Dorrell L, McShane H, Schmidt C, Brooks M, Patel S, Roberts J, Conlon C, Rowland-Jones SL, Bwayo JJ, McMichael AJ, Hanke T. A human immunodeficiency virus 1 (HIV-1) clade A vaccine in clinical trials: stimulation of HIV-specific T-cell responses by DNA and recombinant modified vaccinia virus Ankara (MVA) vaccines in humans. J Gen Virol. 2004 Apr;85(Pt 4):911-919. doi: 10.1099/vir.0.19701-0.
citation: Pancharoen C, Ananworanich J, Thisyakorn U. Immunization for persons infected with human immunodeficiency virus. Curr HIV Res. 2004 Oct;2(4):293-9. doi: 10.2174/1570162043351084.
citation: Shiu C, Cunningham CK, Greenough T, Muresan P, Sanchez-Merino V, Carey V, Jackson JB, Ziemniak C, Fox L, Belzer M, Ray SC, Luzuriaga K, Persaud D; Pediatric AIDS Clinical Trials Group P1059 Team. Identification of ongoing human immunodeficiency virus type 1 (HIV-1) replication in residual viremia during recombinant HIV-1 poxvirus immunizations in patients with clinically undetectable viral loads on durable suppressive highly active antiretroviral therapy. J Virol. 2009 Oct;83(19):9731-42. doi: 10.1128/JVI.00570-09. Epub 2009 Jul 15.