Therapeutic Vaccine for HIV

NCT01859325 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 13014113-I-0141
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- In most people who have human immunodeficiency virus (HIV), the immune system cannot control or cure the infection. Antiretroviral therapy drugs can keep the amount of HIV virus low for a long time. However, this treatment does not remove the virus from the body. In the vast majority of patients antiretroviral therapy also will not protect the body from the virus once treatment stops. Researchers want to see if therapeutic vaccination can help people with HIV. Therapeutic vaccination means giving vaccines to treat an infection that someone already has (HIV, in this case). It may help the body's immune system attack the infection. This study will look at different measures of HIV infection after receiving either therapeutic vaccination or a placebo. Objectives: \- To see whether therapeutic vaccination is safe and can affect how the body responds to HIV infection. Eligibility: \- Individuals between 18 and 65 years of age who have HIV and are taking antiretroviral therapy drugs. Design:

• Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected.
• During the screening visit and throughout the study until week 56, participants will continue to take their HIV medications.
• Participants will be divided into two groups. One group will have the study vaccines. The other will have a placebo.
• The first study vaccine or placebo will be given in weeks 4, 12, and 36. The second study vaccine or the placebo will be given in weeks 24 and 48. Blood samples and other tests will be given at each visit.
• After the study visit at week 56, participants will stop their HIV medications until week 72. From weeks 58 through 72, they will come in every 2 weeks for study visits; each visit will take about 1 hour to complete. These visits will look at the body s response to the vaccines and their HIV viral load. After week 72, participants will re-start their HIV medications.
• There will be follow-up study visits from weeks 76 to 96, with blood tests and other studies.

Conditions

HIV; Therapeutic Vaccine

Keywords

HIV-MAG pDNA Prime; HIV Therapy; Therapeutic Vaccine

Outcome Measures

Primary Outcomes (1)

• The Rate of Related Adverse Events in Subjects Who Began cART During Acute or Early HIV-1 Infection.

  The rate of occurrence of grade 3 or higher AEs, including serious adverse events (SAEs) that per standard criteria (see safety section) are: At least possibly related to the test article, and Definitely NOT related to a factor other than the test article This is to evaluate safety and tolerability of the study vaccines.

  48 weeks

Secondary Outcomes (1)

• HIV-1 Viral Load Following Antiretroviral Treatment Interruption (ATI).

  72 weeks

Study Arms (2)

Vaccine

EXPERIMENTAL

HIV-MAG pDNA vaccine prime will be administered at a dose of 3000 g (1500 g of the HIV-1 gag/pol plasmid and 1500 g of the HIV-1 net/tat/vif, env plasmid) at week 0, 4, 12, and 36. Each construct of HIV-MAG pDNA vaccine (1500 g each) will be mixed and combined with 1000 g of the IL-12 pDNA adjuvant. The resulting mixture will be divided into 2 IM injections and administered as 0.75 mL IM injection in the left deltoid and 0.75 mL IM injection in the right deltoid with EP using the TDS device. IL-12 pDNA adjuvant will be mixed with the HIV-MAG pDNA vaccine prime, as noted above, and administered at a dose of 1000 g (500 g in each IM injection) at week 0, 4, 12, and 36. rVSV HIV gag booster vaccine--The total dose, 1x107 pfu, will be administered as 1 mL (5x106 pfu) IM injection in the left deltoid and 1 mL (5x106 pfu) IM injection in the right deltoid at week 24 and 48.

Biological: rVSV; Biological: IL-12 pDNA adjuvant; Biological: HIV-Mag pDNA

Placebo

PLACEBO COMPARATOR

Placebo for the IL-12 pDNA adjuvant and HIV-MAG pDNA vaccine (sodium chloride for injection, USP 0.9%) will be administered as 0.75 mL IM injection in the left deltoid and 0.75 mL IM injection in the right deltoid at weeks 0, 4, 12, and 36 with EP using the TDS device. Placebo for the rVSV HIV gag (sodium chloride for injection, USP 0.9%) will be administered as 1 mL IM injection in the left deltoid and 1 mL IM injection in the right deltoid at week 24 and 48.

Drug: Placebo

Interventions

rVSV BIOLOGICAL

Attenuated recombinant vesicular stomatitis virus containing HIV-1 gag gene

Vaccine

IL-12 pDNA adjuvant BIOLOGICAL

plasmid DNA containing human IL-12 gene

Vaccine

HIV-Mag pDNA BIOLOGICAL

plasmid DNA vaccine containing genes encoding multiple HIV-1 proteins

Vaccine

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age, 18-65 years.
• Institution of cART within 12 weeks of being diagnosed with acute or early HIV-1 infection.
• Acute HIV-1 infection is defined as:
• Detectable plasma HIV-1 RNA levels of greater than 2000 copies/mL with a negative result from an HIV-1 EIA, or
• Positive result from an HIV-1 EIA with a negative or indeterminate result from an HIV-1 western blot that subsequently evolves to a confirmed positive result, or
• Negative result from an HIV-1 EIA within the past 4 months and HIV-1 RNA levels of greater than 400,000 copies/mL, in the setting of a potential exposure to HIV-1.
• Early HIV-1 Infection is defined as:
• Negative result from an HIV-1 EIA within 6 months prior to a positive result from an HIV-1 EIA and an HIV-1 western blot.
• Negative result from a rapid HIV-1 test within 1 month prior to a positive result from an HIV-1 EIA and an HIV-1 western blot.
• Presence of low level of HIV antibodies as determined by having a positive EIA or a positive Western blot with a non-reactive detuned EIA according to a serologic testing algorithm for recent infection.
• CD4+ cell count greater than 450 cells/mm3 at screening.
• Documentation of continuous cART treatment with suppression of plasma viral level below the limit of detection for greater than 1 year. Subjects with a single blip (i.e., detectable viral levels on cART) prior to randomization may be included provided they satisfy the following criteria:
• The blips are less than 400 copies/mL, and
• Succeeding viral levels return to levels below the limit of detection on subsequent testing.
• Willingness to undergo ATI.

You may not qualify if:

• Allergy to amide-type local anesthetics (bupivacaine (Marcaine), lidocaine (Xylocaine), Mepivacaine (Polocaine/Carbocaine), etidocaine (Duranest), prilocaine (Citanest, EMLA cream).
• Chronic hepatitis B, as evidenced by a positive test for hepatitis B surface antigen (HBsAg), or chronic hepatitis C virus (HCV) infection, as evidenced by a positive test for HCV RNA. Subjects with a positive test for HCV antibody and a negative test for HCV RNA are eligible.
• Changes in cART regimen due to virologic breakthrough.
• HIV immunotherapy or vaccine(s) received within 1 year prior to screening.
• Any licensed or experimental non-HIV vaccination (e.g., hepatitis B, influenza, pneumococcal polysaccharide) received within 4 weeks prior to study entry.
• Interruption of cART for greater than 3 months since its initiation. 8. Any active malignancy that may require systemic chemotherapy or radiation therapy.
• Pregnancy or planned pregnancy during the study period or breastfeeding.
• Any active malignancy that may require systemic chemotherapy or radiationtherapy.
• Immunosuppressive medications received within 6 months before the first study vaccination (Not excluded: (1) corticosteroid nasal spray for allergic rhinitis; (2) topical corticosteroids for mild, uncomplicated dermatitis; or (3) oral/parenteral corticosteroids administered for non-chronic conditions not expected to recur (length of therapy less than or equal to10 days, with completion in greater than or equal to 30 days prior to enrollment).
• Evidence of hepatic decompensation in subjects with cirrhosis: history of ascites, hepatic encephalopathy, or bleeding esophageal varices, or screening laboratory results with any of the following:
• International normalized ratio of greater than or equal to1.5 x ULN.
• Serum albumin less than 3.2 g/dL.
• Serum total bilirubin greater than 1.8 x ULN, unless history of Gilbert's disease or deemed related to treatment with atazanavir.
• History or other clinical evidence of:
• Significant or unstable cardiac disease (e.g., angina, congestive heart failure, recent myocardial infarction, significant arrhythmia).

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Auro Vaccines LLC: collaborator

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Volberding PA, Deeks SG. Antiretroviral therapy and management of HIV infection. Lancet. 2010 Jul 3;376(9734):49-62. doi: 10.1016/S0140-6736(10)60676-9.

  PMID: 20609987 BACKGROUND

• Richman DD, Margolis DM, Delaney M, Greene WC, Hazuda D, Pomerantz RJ. The challenge of finding a cure for HIV infection. Science. 2009 Mar 6;323(5919):1304-7. doi: 10.1126/science.1165706.

  PMID: 19265012 BACKGROUND

• Trono D, Van Lint C, Rouzioux C, Verdin E, Barre-Sinoussi F, Chun TW, Chomont N. HIV persistence and the prospect of long-term drug-free remissions for HIV-infected individuals. Science. 2010 Jul 9;329(5988):174-80. doi: 10.1126/science.1191047.

  PMID: 20616270 BACKGROUND

• Sneller MC, Justement JS, Gittens KR, Petrone ME, Clarridge KE, Proschan MA, Kwan R, Shi V, Blazkova J, Refsland EW, Morris DE, Cohen KW, McElrath MJ, Xu R, Egan MA, Eldridge JH, Benko E, Kovacs C, Moir S, Chun TW, Fauci AS. A randomized controlled safety/efficacy trial of therapeutic vaccination in HIV-infected individuals who initiated antiretroviral therapy early in infection. Sci Transl Med. 2017 Dec 6;9(419):eaan8848. doi: 10.1126/scitranslmed.aan8848.

  PMID: 29212716 RESULT

Related Links

• NIH Clinical Center Detailed Web Page

Results Point of Contact

• Title: Sneller, Michael
• Organization: National Institute of Allergy and Infectious Diseases

MSNELLER@niaid.nih.gov

+1 301 496 0491

Study Officials

• Michael C Sneller, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2013
• First Posted: May 21, 2013
• Study Start: May 10, 2013
• Primary Completion: February 26, 2017
• Study Completion: February 26, 2017
• Last Updated: March 3, 2020
• Results First Posted: April 9, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)