title: Randomized, placebo-controlled phase II trial of heat-killed Mycobacterium vaccae (Longcom batch) formulated as an oral pill (V7).
abstract: One-month Phase II trial was conducted in 43 sputum smear-positive patients with pulmonary tuberculosis randomized into treatment (n = 22) and placebo (n = 21) arms to investigate the safety and efficacy of an orally-administered therapeutic TB vaccine (V7) containing 10 μg of heat-killed Mycobacterium vaccae provided by Longcom company. Immunotherapy and control groups comprised 8 newly diagnosed (1stDx TB; 18.6%), 6 re-treated (RTB; 14%), and 29 multidrug-resistant (MDR-TB; 67.4%) cases distributed at 5:4:13 and 3:2:16 ratios, respectively. Both arms received conventional TB drugs administered under directly observed therapy. The average weight gain in V7 arm was modest, but statistically significant (0.6 kg; p = 0.004), while placebo patients lost 0.1 kg (p = 0.77). Except defervescence and increased lymphocyte percentage, other secondary endpoints such as erythrocyte sedimentation rate (ESR), leukocyte counts and hemoglobin content were not significantly affected. In control patients only one secondary endpoint, ESR, has improved. After one month mycobacterial clearance in sputum smears was observed in 31.8% (p = 0.03) and 9.5% (p = 0.83) of patients on V7 and placebo. However, the difference between outcomes in two arms was below significance threshold (p = 0.07). Thus, larger population of patients with prolonged follow-up is required to support these preliminary findings.
authors.affiliation: Lisichansk Regional Tuberculosis Dispensary; Lisichansk, Ukraine.
authors.forename: Yuri V
authors.initials: YV
authors.lastname: Efremenko
authors.forename: Dmytro A
authors.initials: DA
authors.lastname: Butov
authors.forename: Natalia D
authors.initials: ND
authors.lastname: Prihoda
authors.forename: Svetlana I
authors.initials: SI
authors.lastname: Zaitzeva
authors.forename: Larisa V
authors.initials: LV
authors.lastname: Yurchenko
authors.forename: Nina I
authors.initials: NI
authors.lastname: Sokolenko
authors.forename: Tetyana S
authors.initials: TS
authors.lastname: Butova
authors.forename: Anna L
authors.initials: AL
authors.lastname: Stepanenko
authors.forename: Galyna A
authors.initials: GA
authors.lastname: Kutsyna
authors.forename: Vichai
authors.initials: V
authors.lastname: Jirathitikal
authors.forename: Aldar S
authors.initials: AS
authors.lastname: Bourinbaiar
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009161:Mycobacterium / Q000276:immunology*; D010919:Placebos / Q000008:administration & dosage; D013183:Sputum / Q000382:microbiology; D016896:Treatment Outcome; D032581:Tuberculosis Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000628:therapy*; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D000995:Antitubercular Agents; D010919:Placebos; D032581:Tuberculosis Vaccines; D015164:Vaccines, Inactivated
keywords: DOT; NCT01380119; drug-resistant TB; imm02; immunomodulator; inflammation; mucosa; mycobacterium tuberculosis; therapeutic vaccine