An Evaluation of Immunogenicity and Safety of Two Doses of MVA-nef vs. MVA-BN in HIV-1 Infected Patients

A Single-blind, Randomized, Controlled, Phase II Study to Evaluate Immunogenicity and Safety of Two Doses of the MVA-nef HIV Vaccine in HIV-1 Infected Patients With CD4 > 250/µl

The objective of the study is to compare two doses of MVA-nef vs. MVA-BN to induce Nef-specific cellular immune response in HIV-1 infected patients

Study Overview

• Status: Completed
• Conditions: HIV Infection
• Intervention / Treatment: Biological: MVA-nef; Biological: IMVAMUNE

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Bavaria
    • Erlangen, Bavaria, Germany, 91054
      • University of Erlangen
    • Fuerth, Bavaria, Germany, 90762
      • Doctor's Practice
    • Munich, Bavaria, Germany, 80335
      • Doctor's Practice
    • Munich, Bavaria, Germany, 80801
      • Doctor's Practice
    • Nürnberg, Bavaria, Germany, 90641
      • Doctor's Practice

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ages 18-60
• HIV-1 infection, as documented by any licensed PCR kit or ELISA (confirmed by an complementary assay e.g. Western blot HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA) at any time prior to study entry.
• Stable on HAART for at least 6 consecutive months prior to study entry (changes of one drug for the another drug due to reasons other than virologic failure are allowed)
• Plasma HIV-1 RNA levels of < 50 copies/ml for at least 6 months prior to study entry (two single blips of up to 200 HIV-1 RNA copies/ml are acceptable if they resolve spontaneously without a change in HAART)
• Plasma HIV-1 RNA levels of < 50 copies/ml at study entry
• CD4 nadir >100
• CD4+ cell counts > 250/µl (one measurement within 4 months prior to study entry and one measurement within screening phase)
• For women, negative serum pregnancy test at screening and negative urine or serum pregnancy test within 24 hours prior to vaccination.
• If the volunteer is female and of childbearing potential, she agrees to use an acceptable method of contraception, and not become pregnant for at least 56 days after the last vaccination. A woman is considered of childbearing potential unless post-menopausal or surgically sterilized. (Acceptable contraception methods are restricted to intrauterine contraceptive device; oral contraceptives; diaphragm or condom in combination with contraceptive jelly, cream or foam; Norplant® or DepoProvera®) with use of method for a minimum of 30 days prior to vaccination).
• ALT/SGPT, AST/SGOT, and alkaline phosphatase < 3 times institutional upper limit of normal (ULN).
• Urine protein by dipstick or urinalysis < 100mg/dl or <2+ proteinuria
• CBC: Haemoglobin >8 g/dl; White blood cells greater than 2,500 and less than 11,000/mm3; Platelets greater than or equal to 100,000/mm3
• Read, signed and dated informed consent document after being advised of the risks and benefits of the study in a language able to understand, and prior to performance of any study specific procedure
• Cardiac enzymes: within normal range.

Exclusion Criteria:

• Pregnant or breast-feeding women.
• Administration of any HIV nef vaccine or vaccinia immunization within the past 5 years.
• Uncontrolled serious infection i.e. not responding to antimicrobial therapy.
• History of any serious medical condition, which in the opinion of the investigator would compromise the safety of the subject.
• History of or active autoimmune disease. Persons with vitiligo or thyroid disease on thyroid replacement are not excluded.
• History of malignancy, other than squamous cell or basal cell skin cancer, unless there has been surgical excision that is considered to have achieved cure.
• History or clinical manifestation of clinically significant mental illness or haematological, renal, hepatic, pulmonary, central nervous, cardiovascular or gastrointestinal disorders.
• Any condition which might interfere with study objectives or would limit the subject's ability to complete the study in the opinion of the investigator.
• ECG with clinical significance (complete left or right bundle branch block, or sustained ventricular arrythmia, or 2 PVCs in a row, or ST elevation consistent with ischemia).
• History of myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, or other heart condition under the care of a doctor.

• 3 or more of the following risk factors:

  1. High blood pressure requiring therapy.
  2. High blood cholesterol (> 300 mg/dl or ratio LDL/HDL ≥ 3) not induced by the HIV therapy.
  3. Diabetes mellitus or high blood sugar.
  4. He/she has a first degree relative (for example mother, father, brother, or sister) who had a heart condition before the age of 50.
  5. Smoking cigarettes now.
• History of chronic alcohol abuse (40g / day for at least 6 month) and/or intravenous drug abuse (within the past 6 month).
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
• History of anaphylaxis or severe allergic reaction.
• Acute disease (a moderate or severe illness with or without a fever) at the time of enrolment.
• Any vaccinations with active vaccines within a period starting 30 days prior to administration of the vaccine and ending 30 days after administration of the study vaccine. Any vaccinations with inactive vaccines within a period starting 14 days prior to administration of the vaccine and ending 14 days after administration of the study vaccine.
• Chronic administration (defined as more than 14 days) of immuno- suppressant or immune-modifying drugs during the study period (Corticosteroid nasal sprays are permissible. Subjects who have used topical and inhaled steroids can be enrolled after their therapy is completed).
• Administration or planned administration of immunoglobulins and/or any blood products during a period starting from 3 months prior to administration of the vaccine and ending at study conclusion.
• Use of any investigational or non-registered drug or vaccine other than the study vaccine within 30 days or 7 half-lives (whichever is longer) preceding the first dose of the study vaccine, or planned administration of such a drug during the study period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: 3	Biological: IMVAMUNE; 3 immunizations: 1E8_TCID50 IMVAMUNE
ACTIVE_COMPARATOR: 1; High dose	Biological: MVA-nef; 3 imm.: 5E8_TCID50 MVA-nef, 1E8_TCID50 MVA-nef in non-dominant upper arm
ACTIVE_COMPARATOR: 2; Low dose	Biological: MVA-nef; 3 imm.: 5E8_TCID50 MVA-nef, 1E8_TCID50 MVA-nef in non-dominant upper arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
T-cell response against MVA-BN and the Nef antigen assessed by intracellular cytokine staining assay (ICS)	52 Weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Occurrence, intensity and relationship of adverse events occurring at any time during the study	52 weeks

Collaborators and Investigators

• Sponsor: Bavarian Nordic
• Collaborators: National Institutes of Health (NIH)
• Investigators: Principal Investigator: Thomas Harrer, MD, University of Erlangen, Germany

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Study Completion (ACTUAL): December 1, 2006

Study Registration Dates

• First Submitted: September 12, 2005
• First Submitted That Met QC Criteria: September 12, 2005
• First Posted (ESTIMATE): September 19, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): October 1, 2012
• Last Update Submitted That Met QC Criteria: September 28, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: Treatment Experienced
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections
• Other Study ID Numbers: HIV-NEF-004; HHSN266200400072C (NIAID)