Clinical trial NCT01378312: A Study to Evaluate Safety and Immunogenicity of AERAS-402
Official title: A Phase I Randomized Placebo-Controlled, Double-Blind Study to Evaluate Safety and Immunogenicity of AERAS-402 When Administered to HIV-Negative BCG-Vaccinated Adults Without Evidence of Tuberculosis Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Tuberculosis
Keywords: vaccine
TB
tuberculosis
Lead sponsor: Aeras
Sponsor class: OTHER
First posted: 2011-06-22
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This Phase I study will be conducted as a randomized, double-blind, placebo-controlled study in healthy adult subjects who are HIV-negative, BCG-vaccinated, and have no evidence of tuberculosis infection. The study will be conducted at one clinical research site in India.

The available live tuberculosis vaccine, Bacillus Calmette-Guérin (BCG), provides incomplete protection against pulmonary tuberculosis. For unknown reasons, a BCG revaccination or "booster", while not toxic, does not provide much additional protection. AERAS-402 presents tuberculosis antigens in the setting of a new, live, replication-deficient adenovirus vaccine that may increase T cell-mediated immunity and thus protection from tuberculosis. Since BCG-vaccinated individuals are the population for which AERAS-402 might be indicated, AERAS-402 will be administered to individuals already vaccinated with BCG.


Eligibility criteria: Inclusion Criteria:

* Is male or female
* Is age 18 through 45 years on Study Day 0
* Has completed written informed consent
* Had BCG vaccination at least 5 years ago, documented through medical history or presence of scar
* Has general good health, confirmed by medical history and physical examination
* Has Body Mass Index (BMI) between 19 and 30 (kg/m2)
* Has ability to complete follow-up period of 182 days as required by the protocol
* Females: Ability to avoid pregnancy from 28-days prior to initial study vaccination through the duration of their participation in the study.
* Will commit to avoiding elective surgery for the duration of the study
* Has ability to stay in contact with the investigative site for the duration of the study
* Has completed simultaneous enrollment in Aeras Vaccine Development Registry protocol

Exclusion Criteria:

* Acute illness on the day of randomization
* Oral temperature ≥37.5°C on the day of randomization
* Evidence of significant active infection
* Used immunosuppressive medication within 42 days before entry into the study
* Received immunoglobulin or blood products within 42 days
* Received any investigational drug therapy or vaccine within 182 days
* Received any standard vaccine within 42 days
* Participated in any clinical trial of an investigational adenovirus-based vaccine previously.
* Current chronic drug therapy
* History or laboratory evidence of any past, present or future possible immunodeficiency state which will include (but is not limited to) any laboratory indication of HIV infection
* History of allergic disease or reactions likely to be exacerbated by any component of the study vaccine
* Previous medical history that may compromise the safety of the subject in the study
* Evidence of a new acute illness that may compromise the safety of the subject in the study
* Evidence of chronic hepatitis (e.g., hepatitis B core antibody, or hepatitis C antibody, or other)
* Inability to discontinue daily medications except contraceptives during the study period
* History of alcohol or drug abuse within the past 2 years
* Tobacco or cannabis smoking three or more days per week
* Positive urine test for illicit drugs (opiates, cocaine, amphetamines)
* History or evidence of any systemic disease on physical examination
* History or evidence (including chest X-ray) of active tuberculosis
* Shared a residence within the last year with an individual on anti-tuberculosis treatment or with culture or smear positive tuberculosis
* All females: Positive urine pregnancy test during screening; positive serum pregnancy test on the day of study vaccination; are nursing
* Abnormal (per local laboratory parameters) hemoglobin, hematocrit, white blood cell count, absolute neutrophil count, absolute lymphocyte count, prothrombin time (PT), partial thromboplastin time (PTT), serum creatinine, GGT, ALT, AST, total bilirubin, alkaline phosphatase (ALP), or creatinine drawn within 36 hours prior to randomization.
* Laboratory test evidence of Mtb infection
* Tuberculin skin test evidence of Mtb infection, defined as 15 mm of induration or greater.
* Anal intercourse with another man at least one time (with or without condoms)
* Exchange of goods, money, services or drugs for sex.
* Use of intravenous drugs.
* Sexual intercourse or genital contact within the last 12 months with a known HIV positive individual
* Vaginal intercourse within the last 12 months without use of a condom with a known user of intravenous drugs
* Oral to genital contact within the last 12 months with a known user of intravenous drug
* Vaginal intercourse within the last 12 months without use of a condom with an individual known to have more than one sex partner
* Oral to genital contact within the last 12 months with an individual known to have more than one sex partner

Primary outcomes:
measure: Number and Percentage of Adverse Events by treatment group
timeFrame: Day 56
Secondary outcomes:
measure: Immune Response
timeFrame: Day 182
Other outcomes:
Locations:
city: Bangalore
country: India
facility: Lotus Labs
Study officials:
affiliation: Lotus Labs
name: Vanya Dhagat, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hoft DF, Blazevic A, Stanley J, Landry B, Sizemore D, Kpamegan E, Gearhart J, Scott A, Kik S, Pau MG, Goudsmit J, McClain JB, Sadoff J. A recombinant adenovirus expressing immunodominant TB antigens can significantly enhance BCG-induced human immunity. Vaccine. 2012 Mar 9;30(12):2098-108. doi: 10.1016/j.vaccine.2012.01.048. Epub 2012 Jan 30.