Clinical trial NCT01435135: Study of Late Boost Strategies for HIV-uninfected Participants From Protocol RV 144
Official title: Randomized, Double Blind Evaluation of Late Boost Strategies for HIV-uninfected Participants in the HIV Vaccine Efficacy Trial RV 144: "Aventis Pasteur Live Recombinant ALVAC-HIV (vCP1521) Priming With VaxGen gp120 B/E (AIDSVAX B/E) Boosting in HIV-uninfected Thai Adults"
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: HIV Infections
Lead sponsor: U.S. Army Medical Research and Development Command
Sponsor class: FED
Collaborators: name: National Institutes of Health (NIH)
First posted: 2011-09-15
Enrollment: 162
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to assess safety and tolerability of late boost regimens of AIDSVAX B/E alone, ALVAC-HIV alone, or ALVAC-HIV/AIDSVAX B/E combination in HIV-uninfected participants from RV 144.


Eligibility criteria: Inclusion Criteria:

* Must have participated in RV144, received the active product, and completed all 4 vaccination visits per protocol.
* Must be able to understand and complete the informed consent process.
* Must successfully complete a Test of Understanding prior to enrollment

  * The volunteer must answer 80% or 8 out of 10 of the questions correctly including two compulsory questions answered correctly.
  * If the volunteer is unable to do so, he or she will be given two more opportunities to repeat the TOU.
  * If after three attempts to pass the TOU the volunteer is still unable to do so, the volunteer will become ineligible for study participation.
* Must be in good general health without clinically significant medical history.
* HIV-uninfected per predefined algorithm within 45 days of enrollment.
* Laboratory screening analysis

  * Hemoglobin: Women ≥12.0 g/dL. Men ≥12.5 g/dL
  * White cell count: 4,000 to 11,000 cells/mm3
  * Platelets: 150,000 to 450,000/mm3
  * Normal liver function: ALT/AST ≤1.25 institutional upper limit of reference range
  * Creatinine: ≤1.25 institutional upper limit of reference range
* Urinalysis (dipstick) for blood and protein no greater than 1+, glucose negative
* Female-Specific Criteria:

  * Negative human choriogonadotropin (β-HCG) pregnancy test (urine) for women prior to each vaccination (same day).
  * Be using adequate birth control methods for 45 days prior to the first vaccine/placebo vaccination and will continue to be followed for at least 3 months after the final vaccine/placebo vaccination. Adequate birth control is defined as follows: Contraceptive medications delivered orally, intramuscularly, vaginally, or implanted underneath the skin, surgical methods (hysterectomy or bilateral tubal ligation), condoms, diaphragms, intrauterine device (IUD), abstinence.

Exclusion Criteria:

1. Women breast-feeding or pregnant (positive pregnancy test) or planning to become pregnant during the window between study enrollment and 3 months after the last vaccination visit.

* History of anaphylaxis or other serious adverse reaction to vaccines including to RV 144 vaccines, or allergies or reactions likely to be exacerbated by any component of the vaccine or placebo, including eggs, egg products, streptomycin, or neomycin.
* Subject has received any of the following substances:

  * Chronic use of therapies which may modify immune response, such as IV immune globulin and systemic corticosteroids (in doses of \> 20 mg/day prednisone equivalent for periods exceeding 10 days).
  * The following exceptions are permitted and will not exclude study participation: use of corticosteroid nasal spray for rhinitis, topical corticosteroids for an acute uncomplicated dermatitis; or a short course (duration of 10 days or less, or a single injection) of corticosteroid for a nonchronic condition (based on investigator clinical judgment) at least 2 weeks prior to enrollment in this study.
  * Blood products within 120 days prior to HIV screening.
  * Immunoglobulins within 14 days prior to HIV screening.
  * Any vaccine within 14 days prior to initial study vaccine administration in the present study.
  * Receipt of investigational HIV vaccine product other than the RV 144 regimen.
  * Investigational research agents within 30 days prior to initial study vaccine administration in the present study.
  * Use of anti-tuberculosis prophylaxis or therapy during the past 90 days.
* Any medical, psychiatric, social condition, occupational reason, or other responsibility that, in the judgment of the investigator, is a contraindication to protocol compliance or impairs a subject's ability to give informed consent.
* Psychiatric condition that precludes compliance with the protocol; past or present psychoses; past or present bipolar disorder; disorder requiring lithium; or within 5 years prior to enrollment, a history of suicide plan or attempt.
* Study site employees who are involved in the protocol and/or may have direct access to study related area.

Primary outcomes:
measure: Primary Immunogenicity Endpoint
timeFrame: Week 0
measure: Safety Endpoints
timeFrame: During the 3 days post-vaccination
measure: Primary Immunogenicity Endpoint
timeFrame: Week 2
measure: Primary Immunogenicity Endpoint
timeFrame: Week 24
measure: Primary Immunogenicity Endpoint
timeFrame: Week 26
measure: Primary Immunogenicity Endpoint
timeFrame: Week 48
measure: Primary Immunogenicity Endpoint
timeFrame: Week 72
Secondary outcomes:
measure: Secondary Immunogenicity Endpoints
timeFrame: Baseline, Weeks 2, 24, 26, 48 and 72
Other outcomes:
Locations:
city: Chon Buri
country: Thailand
facility: Bang Lamung District Hospital
city: Chon Buri
country: Thailand
facility: Phan Thong District Hospital
Study officials:
affiliation: Department of Disease Control, Ministry of Public Health, Nonthaburi, Thailand
name: Supachai Rerks-Ngarm, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Kaewkungwal J, Chiu J, Paris R, Premsri N, Namwat C, de Souza M, Adams E, Benenson M, Gurunathan S, Tartaglia J, McNeil JG, Francis DP, Stablein D, Birx DL, Chunsuttiwat S, Khamboonruang C, Thongcharoen P, Robb ML, Michael NL, Kunasol P, Kim JH; MOPH-TAVEG Investigators. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med. 2009 Dec 3;361(23):2209-20. doi: 10.1056/NEJMoa0908492. Epub 2009 Oct 20.
citation: Rerks-Ngarm S, Pitisuttithum P, Excler JL, Nitayaphan S, Kaewkungwal J, Premsri N, Kunasol P, Karasavvas N, Schuetz A, Ngauy V, Sinangil F, Dawson P, deCamp AC, Phogat S, Garunathan S, Tartaglia J, DiazGranados C, Ratto-Kim S, Pegu P, Eller M, Karnasuta C, Montefiori DC, Sawant S, Vandergrift N, Wills S, Tomaras GD, Robb ML, Michael NL, Kim JH, Vasan S, O'Connell RJ; RV305 Study Team. Randomized, Double-Blind Evaluation of Late Boost Strategies for HIV-Uninfected Vaccine Recipients in the RV144 HIV Vaccine Efficacy Trial. J Infect Dis. 2017 Apr 15;215(8):1255-1263. doi: 10.1093/infdis/jix099.
citation: Easterhoff D, Moody MA, Fera D, Cheng H, Ackerman M, Wiehe K, Saunders KO, Pollara J, Vandergrift N, Parks R, Kim J, Michael NL, O'Connell RJ, Excler JL, Robb ML, Vasan S, Rerks-Ngarm S, Kaewkungwal J, Pitisuttithum P, Nitayaphan S, Sinangil F, Tartaglia J, Phogat S, Kepler TB, Alam SM, Liao HX, Ferrari G, Seaman MS, Montefiori DC, Tomaras GD, Harrison SC, Haynes BF. Boosting of HIV envelope CD4 binding site antibodies with long variable heavy third complementarity determining region in the randomized double blind RV305 HIV-1 vaccine trial. PLoS Pathog. 2017 Feb 24;13(2):e1006182. doi: 10.1371/journal.ppat.1006182. eCollection 2017 Feb.