Phase IIb randomized trial of adjunct immunotherapy in patients with first-diagnosed tuberculosis, relapsed and multi-drug-resistant (MDR) TB

Placebo-controlled, randomized, phase 2b trial was conducted in 34 adults comprising 18 first-diagnosed (52.9%), 6 relapsed (17.6%), and 10 MDR-TB (29.4%) cases to investigate the safety and efficacy of an oral immune adjunct (V5). The immunotherapy (N = 24) and placebo (N = 10) arms received once-daily tablet of V5 or placebo for one month in addition to conventional anti-TB therapy (ATT) administered under directly observed therapy (DOT). The enlarged liver, total bilirubin, erythrocyte sedimentation rate, lymphocyte and leukocyte counts improved significantly in V5 recipients (P = 0.002; 0.03; 8.3E-007; 2.8E-005; and 0.002) but remained statistically unchanged in the placebo group (P = 0.68; 0.96; 0.61; 0.91; and 0.43 respectively). The changes in hemoglobin and ALT levels in both treatment arms were not significant. The body weight increased in all V5-treated patients by an average 3.5 ± 1.8 kg (P = 2.3E-009), while 6 out of 10 patients on placebo gained mean 0.9 ± 0.9 kg (P = 0.01). Mycobacterial clearance in sputum smears was observed in 78.3% and 0% of patients on V5 and placebo (P = 0.009). The conversion rate in V5-receiving subjects with MDR-TB (87.5%) seemed to be higher than in first-diagnosed TB (61.5%) but the difference was not significant (P = 0.62). Scoring of sputum bacillary load (range 3-0) at baseline and post-treatment revealed score reduction in 23 out of 24 (95.8%) V5 recipients (from mean/median 2.2/3 to 0.3/0; P = 6E-010) but only in 1 out of 10 (10%) patients on placebo (1.9/1.5 vs. 1.8/1; P = 0.34). No adverse effects or TB reactivation were seen at any time during follow-up. V5 is safe as an immune adjunct to chemotherapeutic management of TB and can shorten substantially the duration of treatment.