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Safety, tolerability, and immunogenicity of the novel antituberculous vaccine RUTI: randomized, placebo-controlled phase II clinical trial in patients with latent tuberculosis infection.

Nell AS, D'lom E, Bouic P, Sabaté M, Bosser R, Picas J, Amat M, Churchyard G, Cardona PJ - PLoS ONE (2014)

Bottom Line: Assessment of safety showed no deaths during study.These events were mostly mild and well tolerated.The best polyantigenic response was obtained when administrating 25 µg RUTI, especially in HIV-positive subjects which was not increased after the second inoculation.

View Article: PubMed Central - PubMed

Affiliation: PAREXEL Early Phase Clinical Unit, Bloemfontein, South Africa.

ABSTRACT

Objectives: 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.

Methods and findings: 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.

Conclusion: 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.

Trial registration: ClinicalTrials.gov NCT01136161.

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Study design of the clinical trial.
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pone-0089612-g002: Study design of the clinical trial.

Mentions: Each subject was randomized to receive one of the four treatments: placebo, 5, 25 or 50 µg (two subcutaneous administrations of 0.3 mL of the same treatment, at deltoid muscle area of alternate arms, 28 Days apart) [Fig. 1]. Each vial of placebo contents: sucrose (50,000.0 µg/mL), soy lecithin (2,114.4 µg/mL), sodium cholate 230.0 µg/mL and sodium chloride 52.1 µg/mL, which is exactly the same composition of RUTI vaccine, excepting the content of drug substance. (FCMtb). Subjects were monitored until one month after the second inoculation with RUTI (Fig. 2).


Safety, tolerability, and immunogenicity of the novel antituberculous vaccine RUTI: randomized, placebo-controlled phase II clinical trial in patients with latent tuberculosis infection.

Nell AS, D'lom E, Bouic P, Sabaté M, Bosser R, Picas J, Amat M, Churchyard G, Cardona PJ - PLoS ONE (2014)

Study design of the clinical trial.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3935928&req=5

pone-0089612-g002: Study design of the clinical trial.
Mentions: Each subject was randomized to receive one of the four treatments: placebo, 5, 25 or 50 µg (two subcutaneous administrations of 0.3 mL of the same treatment, at deltoid muscle area of alternate arms, 28 Days apart) [Fig. 1]. Each vial of placebo contents: sucrose (50,000.0 µg/mL), soy lecithin (2,114.4 µg/mL), sodium cholate 230.0 µg/mL and sodium chloride 52.1 µg/mL, which is exactly the same composition of RUTI vaccine, excepting the content of drug substance. (FCMtb). Subjects were monitored until one month after the second inoculation with RUTI (Fig. 2).

Bottom Line: Assessment of safety showed no deaths during study.These events were mostly mild and well tolerated.The best polyantigenic response was obtained when administrating 25 µg RUTI, especially in HIV-positive subjects which was not increased after the second inoculation.

View Article: PubMed Central - PubMed

Affiliation: PAREXEL Early Phase Clinical Unit, Bloemfontein, South Africa.

ABSTRACT

Objectives: 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.

Methods and findings: 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.

Conclusion: 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.

Trial registration: ClinicalTrials.gov NCT01136161.

Show MeSH
Related in: MedlinePlus