title: Safety, tolerability, and immunogenicity of the novel antituberculous vaccine RUTI: randomized, placebo-controlled phase II clinical trial in patients with latent tuberculosis infection.
abstract: OBJECTIVE
  To evaluate the safety, tolerability and immunogenicity of three different doses (5, 25 and 50 µg) of the novel antituberculous vaccine RUTI compared to placebo in subjects with latent tuberculosis infection.
  
  
  RESULTS
  Double-blind, randomized, placebo-controlled Phase II Clinical Trial (95 patients randomized). Three different RUTI doses and placebo were tested, randomized both in HIV-positive (n = 47) and HIV-negative subjects (n = 48), after completion of one month isoniazid (INH) pre-vaccination. Each subject received two vaccine administrations, 28 Days apart. Five patients withdrew and 90 patients completed the study. Assessment of safety showed no deaths during study. Two subjects had serious adverse events one had a retinal detachment while taking INH and was not randomized and the other had a severe local injection site abscess on each arm and was hospitalized; causality was assessed as very likely and by the end of the study the outcome had resolved. All the patients except 5 (21%) patients of the placebo group (3 HIV+ and 2 HIV-) reported at least one adverse event (AE) during the study. The most frequently occurring AEs among RUTI recipients were (% in HIV+/-): injection site reactions [erythema (91/92), induration (94/92), local nodules (46/25), local pain (66/75), sterile abscess (6/6), swelling (74/83), ulcer (20/11), headache (17/22) and nasopharyngitis (20/5)]. These events were mostly mild and well tolerated. Overall, a polyantigenic response was observed, which differed by HIV- status. The best polyantigenic response was obtained when administrating 25 µg RUTI, especially in HIV-positive subjects which was not increased after the second inoculation.
  
  
  CONCLUSIONS
  This Phase II clinical trial demonstrates reasonable tolerability of RUTI. The immunogenicity profile of RUTI vaccine in LTBI subjects, even being variable among groups, allows us considering one single injection of one of the highest doses in future trials, preceded by an extended safety clinical phase.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01136161.
authors.affiliation: PAREXEL Early Phase Clinical Unit, Bloemfontein, South Africa.
authors.forename: Andre S
authors.initials: AS
authors.lastname: Nell
authors.affiliation: PAREXEL International, Madrid, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: D'lom
authors.affiliation: Synexa Life Sciences, Cape Town, South Africa.
authors.forename: Patrick
authors.initials: P
authors.lastname: Bouic
authors.affiliation: TFS Develop, Barcelona, Catalonia, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Sabaté
authors.affiliation: Janus Developments, Barcelona, Catalonia, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Bosser
authors.affiliation: Archivel Farma, Badalona, Catalonia, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Picas
authors.affiliation: Archivel Farma, Badalona, Catalonia, Spain.
authors.forename: Mercè
authors.initials: M
authors.lastname: Amat
authors.affiliation: The Aurum Institute, Johannesburg, South Africa.
authors.forename: Gavin
authors.initials: G
authors.lastname: Churchyard
authors.affiliation: Archivel Farma, Badalona, Catalonia, Spain ; Unitat de Tuberculosi Experimental (UTE), Institut per a la Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Catalonia, Spain.
authors.forename: Pere-Joan
authors.initials: PJ
authors.lastname: Cardona
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006678:HIV / Q000302:isolation & purification; D015658:HIV Infections / Q000150:complications / Q000276:immunology / Q000821:virology; D006801:Humans; D055985:Latent Tuberculosis / Q000209:etiology* / Q000628:therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011379:Prognosis; D012449:Safety; D032581:Tuberculosis Vaccines / Q000276:immunology* / Q000627:therapeutic use*; D014611:Vaccination
chemical_list: D032581:Tuberculosis Vaccines