Clinical trial NCT00412477: A Phase I Study of Safety and Immunogenicity of the WRAIR HIV-1 Vaccine
Official title: RV 151: A Phase I Study of Safety and Immunogenicity of the WRAIR HIV-1 Vaccine LFn-p24 Administered by the Intramuscular (IM) Route in Healthy Adults, WRAIR #984, HSRRB Log # A-11905.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: HIV
Lfn-p24
Anthrax
IM
HIV-1
HIV Preventive Vaccine
Lead sponsor: U.S. Army Medical Research and Development Command
Sponsor class: FED
Collaborators: name: Walter Reed Army Institute of Research (WRAIR)
First posted: 2006-12-18
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: To evaluate the safety of LFn-p24 administered at three different doses with Alhydrogel given intramuscularly

To evaluate immune responses to LFn-p24 with Alhydrogel at three different doses given intramuscularly

Detailed description: The study seeks to enroll healthy, vaccine naïve volunteers, 18 through 45 years old. Recruitment consists of using flyers, newspaper advertising, radio, and direct mailing at local military installations, targeting the general population of the greater Washington D.C. area.

The study's primary objective is the safety and tolerability of Lfn-p24 given IM.

Volunteers will be screened (visit 1) and enrolled within 2 to 12 weeks prior to the first vaccination. Study volunteers will receive a briefing from the Principal Investigator (PI) or a sub investigator. The briefing is followed by an opportunity for questions from the volunteers. The PI or designee will then review the consent form with potential volunteers (visit 1) and answer any questions. After review, an Informed Consent will be signed and a "Test of Understanding" will be completed by all volunteers, prior to enrollment in the study. A second pre-screening visit (visit 2) will occur 3 - 30 days prior to the first vaccination (visit 3) to confirm eligibility for vaccination. During this visit each volunteer will have an opportunity to ask questions about the study.

On the day of vaccination (visits 3, 6, and 10), volunteers will be observed for 30 minutes following injection for acute adverse experiences and will be contacted the day following injection for a brief adverse reaction interview. In addition, volunteers will complete diaries for 7 days following each vaccination and will be evaluated by a clinical investigator if significant symptoms are reported. Adverse effects and laboratory abnormalities will be tabulated. Routine measurements of hematology, serum chemistry, and urinalysis laboratory tests will be performed in subsequent safety and general follow up visits.renee

LFn-p24 with Alhydrogel adjuvant will be delivered IM in the deltoid muscle at the intervals shown below. Groups will be enrolled in staggered fashion beginning with the lowest dose group. The subsequent groups receiving higher doses will then be enrolled by the investigator if the second injection of the immediate lower dose is shown to be safe and well tolerated (\< grade II toxicity), after the 2 week post vaccination follow-up visit.

IMMUNIZATION SCHEDULE

Group I Subjects \*6 0:150µg LFn-p24 Alhydrogel;4th Week:150µg LFn-p24 Alhydrogel; 16th Week:150µg LFn-p24 Alhydrogel; Group II Subjects \*6 0:300µg LFn-p24 Alhydrogel; 4th Week: 300µg LFn-p24 Alhydrogel; 16th Week: 300µg LFn-p24 Alhydrogel; Group III Subjects \*6 0: 450µg LFn-p24 Alhydrogel; 4th Week: 450µg LFn-p24 Alhydrogel; 16th Week: 450µg LFn-p24 Alhydrogel

\*Six subjects per group includes 4 vaccines and 2 placebos.

Eligibility criteria: Inclusion Criteria:

* Citizens of the U.S.A. who are not at high-risk for HIV infection.
* Age: 18 through 45 years of age.
* For women, negative serum pregnancy test will be required within two days prior to any injection, as well as verbal assurance that adequate contraceptive measures are applied.
* Good health as determined by medical history, physical examination, and clinical judgment.

Clinical laboratory values at screening within the following ranges:

* Hematocrit: Women: \> 34%: Men \>38% (Mild anemia in any potential trial volunteer who is otherwise healthy attributable by appropriate laboratory studies to thalassemia minor will not be cause for exclusion)
* White blood cell count: 3,000 to 12,000 cells/mm3
* Platelets: 125,000 to 550,000 per mm3
* Chemistry Panel: Expanded chemistry panel within institutional normal ranges or accompanied by site physician approval.
* Urine dipstick for protein and blood: negative or trace. If either is ≥ 1+, obtain complete urinalysis (UA). If microscopic UA confirms evidence of hematuria or proteinuria ≥ 1+, the volunteer is ineligible unless menstruating, then a repeat UA is required.
* Negative serology for HIV infection (ELISA test).
* Availability for at least 52 weeks
* Successful completion of the Test of Understanding, Commitment for Trial Participation and signature of the approved Trial Consent Form.

Exclusion Criteria:

* Acknowledge engaging in highest-risk behavior within 48 weeks of study entry: (i.e., active injecting drug use or having sexual intercourse with a known HIV-1 infected partner).
* Have active tuberculosis or other systemic infectious process by review of systems and physical examination.
* Have a history of immunodeficiency, chronic illness requiring continuous or frequent medical intervention, autoimmune disease, or use of immunosuppressive medications.
* Have evidence of psychiatric, medical and/or substance abuse problems during the past 48 weeks that the investigator believes would adversely affect the volunteer's ability to participate in the trial.
* Have occupational or other responsibilities that would prevent completion of participation in the study.
* Have received any live, attenuated vaccine within 60 days of study entry.
* NOTE: Medically indicated subunit or killed vaccines (e.g., Hepatitis A or Hepatitis B) are not exclusionary but should be given at least 2 weeks before or after HIV immunization to avoid potential confusion of adverse reactions.
* Acute or chronic Hepatitis caused by viral or other etiology.
* Have used experimental therapeutic agents within 30 days of study entry.
* Have received blood products or immunoglobulins in the past 12 weeks.
* Have a history of anaphylaxis or other serious adverse reactions to vaccines.
* Have previously received an HIV and/or anthrax vaccine.
* Currently enrolled in other vaccine trials.
* Are pregnant or lactating.
* NOTE: Women of child-bearing potential must be using effective contraception from the date of enrollment into the protocol.
* Have an immediate type hypersensitivity reaction to aminoglyocides, e.g., kanamycin (used to prepare the LFn-p24 vaccine).
* Are study site employees who are involved in the protocol and may have direct access to the immunogenicity results.
* Are receiving ongoing therapy with immunosuppressive therapy such as systemic corticosteroids or cancer chemotherapy.
* Are active duty military or reserves.

Primary outcomes:
measure: Humoral: Responders to ELISA and Western Blot antibodies to HIV-1 subtype B gag p24
timeFrame: Days 0, 14, 42, 70, 126, 182, 252 and 364
measure: Cellular: Cytotoxic T-lymphocyte (CTL) responses against subtype B gag antigen target expressed in Epstein Barr Virus (EBV) transformed autologous B cell lines.
timeFrame: Days 3, 14, 42, 70, 126, 182, 252, and 364
measure: IFN-y ELISPOT assay against HIV-gag antigen.
timeFrame: Days 3, 14, 42, 70, 126, 182, 252, and 364
measure: IFN- ICS assay against HIV-gag antigen.
timeFrame: Days 3, 14, 42, 70, 126, 182, 252, and 364
measure: Lymphocyte proliferative responses to HIV-1 subtype B gag
timeFrame: Days 3, 14, 42, 70, 126, 182, 252, and 364
Secondary outcomes:
measure: Humoral- Binding antibodies to LFn
timeFrame: Days 3, 14, 42, 70, 126, 182, 252, and 364
measure: Neutralizing antibodies to LFn
timeFrame: Days 3, 14, 42, 70, 126, 182, 252, and 364
measure: Cellular: Lymphoproliferation to LFn
timeFrame: Days 3, 14, 42, 70, 126, 182, 252, and 364
Other outcomes:
measure: and Systemic Reactions After Immunization of of Lfn-p24 Given IM
timeFrame: 30 minutes and 7 days post vaccination
Locations:
city: Rockville
country: United States
facility: Vaccine Clinical Research Center
state: Maryland
Study officials:
affiliation: Walter Reed Army Institute of Research (WRAIR)
name: CDR Shirley Lee-Lecher, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 1. UNAIDS/WHO. Report on the global HIV/AIDS epidemic.June 2000. 2. Quinn TC. Global burden of the HIV pandemic. Lancet.1996;348:99-106. 3. Moss B. Genetically engineered poxviruses for recombinant gene expression, vaccination, and safety. PNAS 1996;93; 11341-8. 4. Tartaglia J, Excler JL, El Habib R, Limbach K, Meignier B, Plotkin S, Klein M. Canarypoxvirus-based vaccines : prime-boost strategies to induce cell-mediated and humoral immunity against HIV. AIDS Res Hum Retroviruses 1998;14(supp.3): S291-S298. 5. Girard M, Excler JL. Human Immunodeficiency virus. In Vaccines. Plotkin SA and Mortimer EA Eds. Saunders, Philadelphia,1999, pp.928-967. 6. Excler J-L, Plotkin S. The prime-boost concept applied to HIV preventive vaccines. AIDS 1997;11(suppl A):S127-137. 7. Ogg GS, Jin X, Bonhoeffer S, Dunbar PR, Nowak MA, Mopnard S, Segal JP, Cao Y, 8. Rowland-Jones SL, Cerundolo V, Hurley A, Markowwitz M, Ho DD, Nixon DF, McMichael AJ. Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral RNA. Science 1998; 279: 2103-6. 8. Schmitz JE, Kuroda MJ, Santra S, Sasseville VG, Simon MA, Lifton MA, Racz P, Tenner-Racz K, Dalesandro M, Scallon BJ, Ghrayeb J, Forman MA, Montefiori DC, Rieber EP, Letvin NL, Reimann KA. Control of viremia in simian immunodeficiency virus infection by CD8 lymphocytes. Science 1999; 283: 857-60. 9. Brodie SJ, Lewinsohn DA, Patterson BK, Jiyamapa D, Krieger J, Corey L, Greenberg P, Riddell SR. In vivo migration and function of transferred HIV-1-specific cytotoxic T cells. Nature Medicine 1999; 5: 34-41. 10. Letvin NL. Progress in development of an AIDS vaccine. Science 1998; 280: 1875-9.