Safety, Tolerability, and Immunogenicity of the Novel Antituberculous Vaccine RUTI : Randomized, Placebo-Controlled Phase II Clinical Trial in Patients with Latent Tuberculosis Infection
Nell, Andre S. (PAREXEL Early Phase Clinical Unit, Bloemfontein, South Africa)
D'lom, Eva (PAREXEL International, Madrid, Spain)
Bouic, Patrick (Synexa Life Sciences, Cape Town, South Africa)
Sabaté, Montserrat (TFS Develop, Barcelona, Catalonia, Spain)
Bosser, Ramon (Janus Developments (Barcelona, Catalunya))
Picas, Jordi (Archivel Farma)
Amat, Mercè (Archivel Farma)
Churchyard, Gavin (The Aurum Institute, Johannesburg, South Africa)
Cardona, Pere-Joan (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Universitat Autònoma de Barcelona

Date:	2014
Abstract:	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. 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. 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.
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Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	PloS one, Vol. 9 (february 2014) , ISSN 1932-6203

DOI: 10.1371/journal.pone.0089612
PMID: 24586912

10 p, 1.1 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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