Clinical trial NCT00189930: An Evaluation of Immunogenicity and Safety of Two Doses of MVA-nef vs. MVA-BN in HIV-1 Infected Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infection
Keywords: Treatment Experienced
Lead sponsor: Bavarian Nordic
Sponsor class: INDUSTRY
Collaborators: name: National Institutes of Health (NIH)
First posted: 2005-09-19
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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.

Primary outcomes:
measure: T-cell response against MVA-BN and the Nef antigen assessed by intracellular cytokine staining assay (ICS)
timeFrame: 52 Weeks
Secondary outcomes:
measure: Occurrence, intensity and relationship of adverse events occurring at any time during the study
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Erlangen
country: Germany
facility: University of Erlangen
state: Bavaria
city: Fuerth
country: Germany
facility: Doctor's Practice
state: Bavaria
city: Munich
country: Germany
facility: Doctor's Practice
state: Bavaria
city: Munich
country: Germany
facility: Doctor's Practice
state: Bavaria
city: Nürnberg
country: Germany
facility: Doctor's Practice
state: Bavaria
Study officials:
affiliation: University of Erlangen, Germany
name: Thomas Harrer, MD
role: PRINCIPAL_INVESTIGATOR
References: