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

HIV Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00189930
• Other study ID #: HIV-NEF-004
• Secondary ID: HHSN266200400072
• Status: Completed
• Phase: Phase 2
• First received: September 12, 2005
• Last updated: September 28, 2012
• Start date: April 2005
• Est. completion date: December 2006

Study information

• Verified date: September 2012
• Source: Bavarian Nordic
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-Institut
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 77
• Est. completion date: December 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infection

Intervention

Biological:
• MVA-nef
3 imm.: 5E8_TCID50 MVA-nef, 1E8_TCID50 MVA-nef in non-dominant upper arm
• IMVAMUNE
3 immunizations: 1E8_TCID50 IMVAMUNE

Locations

Country	Name	City	State
Germany	University of Erlangen	Erlangen	Bavaria
Germany	Doctor's Practice	Fuerth	Bavaria
Germany	Doctor's Practice	Munich	Bavaria
Germany	Doctor's Practice	Munich	Bavaria
Germany	Doctor's Practice	Nürnberg	Bavaria

Sponsors (2)

Lead Sponsor	Collaborator
Bavarian Nordic	National Institutes of Health (NIH)

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	T-cell response against MVA-BN and the Nef antigen assessed by intracellular cytokine staining assay (ICS)		52 Weeks	No
Secondary	Occurrence, intensity and relationship of adverse events occurring at any time during the study		52 weeks	No