A Phase I Study of Safety and Immunogenicity of the WRAIR HIV-1 Vaccine

NCT00412477 | Completed Phase 1 FDA Drug

• 2 other identifiers: WRAIR 984HSRRB Log # A-11905
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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

Conditions

HIV Infections

Keywords

HIV; Lfn-p24; Anthrax; IM; HIV-1; HIV Preventive Vaccine

Outcome Measures

Primary Outcomes (5)

• Humoral: Responders to ELISA and Western Blot antibodies to HIV-1 subtype B gag p24

  An HIV-I enzyme linked immunosorbent assay (ELISA) assay will be performed as designated throughout the course of the protocol during Visits 1 through 15. If the ELISA is reactive it will be repeated and an FDA- approved HIV Western blot will be performed. If the Western blot is positive, HIV molecular diagnostics (Roche Amplicor) will be performed

  Days 0, 14, 42, 70, 126, 182, 252 and 364

• Cellular: Cytotoxic T-lymphocyte (CTL) responses against subtype B gag antigen target expressed in Epstein Barr Virus (EBV) transformed autologous B cell lines.

  Cytotoxic T-lymphocyte (CTL) responses against subtype B gag antigen target expressed in Epstein Barr Virus (EBV) transformed autologous B cell lines. Bulk CTL is currently defined to be positive if the HIV-1 antigen expressing targets relative to control have a specific lysis 10%. CD8+ CTL occurs when lytic activity decreases by 50% after removal of CD8 cells, while removal of CD4 cells maintains specific lysis at 5%. An analogous rule is applied for CD4+ CTL

  Days 3, 14, 42, 70, 126, 182, 252, and 364

• IFN-y ELISPOT assay against HIV-gag antigen.

  IFN-y ELISPOT assay using a panel of B clade gag peptides. A positive responder will be defined in accordance with other HIV Vaccine Trial Network (HVTN) definitions. For example a positive response may be defined by a significant difference between the number of IFN-g spot forming cell s (SFC)/million peripheral blood mononuclear cells (PBMC) in the presence of HIV gag antigen and no antigen. Other arbitrary definitions may be used.

  Days 3, 14, 42, 70, 126, 182, 252, and 364

• IFN- ICS assay against HIV-gag antigen.

  For the IFN-gamma intracellular cytokine staining (ICS) assay we will use a panel of B clade gag peptides or other appropriate gag antigens. A positive responder will be defined in accordance with the HIV Vaccine Trial Network (HVTN) definitions or other definitions as appropriate. For example a positive response may be defined as a two-fold difference between the percentage of CD3+CD8+IFN-y+ or CD3+CD4+IFN-y+ T cells in the presence of HIV gag antigen compared with no antigen

  Days 3, 14, 42, 70, 126, 182, 252, and 364

• Lymphocyte proliferative responses to HIV-1 subtype B gag

  Lymphocyte proliferative responses to HIV- I subtype B gag p24. The data are expressed as a Lymphocyte Stimulation Index (LSI)= (PBMC cpm + antigen/ mitogen) I (PBMC cpm+ medium)\] to define antigen specificity. Individuals are arbitrarily designated as responders non-responders if their LSI is greater than or equal to 5.

  Days 3, 14, 42, 70, 126, 182, 252, and 364

Secondary Outcomes (3)

• Humoral- Binding antibodies to LFn

  Days 3, 14, 42, 70, 126, 182, 252, and 364

• Neutralizing antibodies to LFn

  Days 3, 14, 42, 70, 126, 182, 252, and 364

• Cellular: Lymphoproliferation to LFn

  Days 3, 14, 42, 70, 126, 182, 252, and 364

Other Outcomes (1)

• and Systemic Reactions After Immunization of of Lfn-p24 Given IM

  30 minutes and 7 days post vaccination

Study Arms (3)

Group 1 - LFn-p24 ISOug with Alhydrogel

EXPERIMENTAL

HIV LFn-p24 is a combination of an Anthrax derived polypeptide Lethal factor (LFn), from which the toxin domain has been removed, and the HIV-1 gag p24 protein has been fused to LFn. Lfn-p24 is formulated in liquid form, and vialed. Product is administered IM, 1ml. Six subjects (4 vaccines and 2 placebos). Placebo recipients will receive a saline preparation in similar volume given IM. Immunizations given at 0, 4 and 16 weeks

Biological: HIV LFn-p24

Group 2 - LFn-p24 300ug with Alhydrogel

EXPERIMENTAL

HIV LFn-p24 is a combination of an Anthrax derived polypeptide Lethal factor (LFn), from which the toxin domain has been removed, and the HIV-1 gag p24 protein has been fused to LFn. Lfn-p24 is formulated in liquid form, and vialed. Product is administered IM, 1ml. Six subjects (4 vaccines and 2 placebos). Placebo recipients will receive a saline preparation in similar volume given IM. Immunizations given at 0, 4 and 16 weeks

Biological: HIV LFn-p24

Group 3 - LFn-p24 450ug with Alhydrogel

EXPERIMENTAL

HIV LFn-p24 is a combination of an Anthrax derived polypeptide Lethal factor (LFn), from which the toxin domain has been removed, and the HIV-1 gag p24 protein has been fused to LFn. Lfn-p24 is formulated in liquid form, and vialed. Product is administered IM, 1ml. Six subjects (4 vaccines and 2 placebos). Placebo recipients will receive a saline preparation in similar volume given IM. Immunizations given at 0, 4 and 16 weeks

Biological: HIV LFn-p24

Interventions

HIV LFn-p24 BIOLOGICAL

HIV LFn-p24 is a combination of an Anthrax derived polypeptide Lethal factor (LFn), from which the toxin domain has been removed, and the HIV-1 gag p24 protein has been fused to LFn. Lfn-p24 is formulated in liquid form, and vialed at 200 µg/ml and 600 µglml. The product will be administered IM in doses ranging from 150µg to 450µg with Alhydrogel.

Group 1 - LFn-p24 ISOug with Alhydrogel; Group 2 - LFn-p24 300ug with Alhydrogel; Group 3 - LFn-p24 450ug with Alhydrogel

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• U.S. Army Medical Research and Development Command: lead
• Walter Reed Army Institute of Research (WRAIR): collaborator

Study Sites (1)

Vaccine Clinical Research Center

Rockville, Maryland, 20850, United States

Location

Related Publications (1)

• 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.

  BACKGROUND

MeSH Terms

Conditions

HIV Infections; Anthrax

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Bacillaceae Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Study Officials

• CDR Shirley Lee-Lecher, MD

  Walter Reed Army Institute of Research (WRAIR)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2006
• First Posted: December 18, 2006
• Study Start: August 20, 2004
• Primary Completion: March 13, 2006
• Study Completion: November 1, 2006
• Last Updated: October 10, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)