Open-label Phase II clinical trial in 75 patients with advanced hepatocellular carcinoma receiving daily dose of tableted liver cancer vaccine, hepcortespenlisimut-L.

BACKGROUND: An increasing number of studies is now devoted to immunotherapy of cancer. We evaluated the clinical benefit of hepcortespenlisimut-L (Hepko-V5 [formerly known as V5])-an oral therapeutic vaccine designated by the United States Food and Drug Administration (FDA) as an orphan drug for treatment of hepatocellular carcinoma (HCC). V5 was initially developed by us in 2002 to treat hepatitis B or C viral infections and liver cirrhosis. METHODS: The outcome of open-label Phase II trial of daily dose of V5 pill was analyzed retrospectively. Over a period of 5 years, 75 patients with advanced HCC were enrolled, consisting of 29 (38.7%) females and 46 (61.3%) males with a median age of 60 years (mean 61.6±8.1 years). Out of these, 23 (30.7%) had hepatitis B and 34 (45.3%) had hepatitis C infections, including 9 (12%) with dual infection, 4 (5.3%) negative for both viruses, and 5 (6.7%) without established viral diagnosis. Most patients (94.7%) had underlying liver cirrhosis of varying severity. RESULTS: After a median of 2 months of treatment, 50 out of 75 patients had experienced a decline in serum levels of the tumor marker, alpha-fetoprotein (AFP) (66.7%; P=0.006 by Wilcoxon signed rank test). Baseline median AFP levels were 245.2 IU/mL (mean 4,233; range 7.2-92,407; 95% confidence interval [CI] 1,186-7,280) and post-treatment values were 102.3 IU/mL (mean 2,539; range 0.9-54,478; 95% CI 503-4,575). The decrease in AFP was correlated either with tumor clearance or regression on computed tomography scans. The median overall survival time could not be established since 68 out of 75 (90.7%) patients were still alive after median follow-up of 12 months (mean 15±9.7; range 7-59; 95% CI 12.8-17.2). The first patient in this study received immunotherapy 5 years ago and still remains in complete remission. None of the patients experienced any serious adverse effects or toxicity. CONCLUSION: The results indicate that hepcortespenlismut-L is a safe, effective, and fast-acting immunomodulatory intervention for HCC. The Phase III, randomized, double-blind, placebo-controlled trial is now initiated at the Mongolian National Cancer Center to confirm these promising findings.

Double-blind, placebo-controlled, 1:1 randomized Phase III clinical trial of Immunoxel honey lozenges as an adjunct immunotherapy in 269 patients with pulmonary tuberculosis.

AIM: Safer and shorter antituberculosis treatment (ATT) regimens represent the unmet medical need. PATIENTS & METHODS: The patients were randomly assigned into two arms: the first (n = 137) received once-daily sublingual honey lozenge formulated with botanical immunomodulator Immunoxel and the second (n = 132) received placebo lozenges along with conventional ATT. Immunoxel and placebo arms were demographically similar: 102 versus 106 had drug-susceptible TB; 28 versus 20 multidrug-resistant TB (MDR-TB); 7 versus 7 extensively drug-resistant TB (XDR-TB); and 22 versus 20 TB-HIV. The primary end point was sputum smear conversion. RESULTS: After 1 month 87 out 132 (65.9%) of Immunoxel recipients became sputum smear negative, whereas 32 out of 127 (25.2%) in placebo group had converted (p < 0.0001). Sputum clearance produced by Immunoxel was equally effective across all forms of TB. In the immunotherapy arm the average weight gain was 2 kg, but placebo recipients gained only 0.6 kg. Immunoxel reduced TB-associated inflammation as evidenced by defervescence and normalization of elevated leukocyte counts and erythrocyte sedimentation rate. No adverse effects were seen at any time. The liver function tests indicate that ATT-caused hepatotoxicity was counteracted by Immunoxel. These results are in agreement with prior 20 trials of Immunoxel conducted over the past 17 years. CONCLUSION: Immunoxel is affordable, safe, effective, fast-acting, commercially available immunotherapeutic intervention to supplement conventional TB chemotherapy. Clinicaltrials.gov ID: NCT01061593.

Adjunct oral immunotherapy in patients with re-treated, multidrug-resistant or HIV-coinfected TB.

This Phase IIb, placebo-controlled study involved 55 TB patients treated with anti-TB therapy. They were divided into two groups, matched by age, gender, baseline bodyweight and clinical manifestations: one group (n = 27) received a once-daily V-5 Immunitor (V5) immunotherapy pill and the other (n = 28) received placebo. Only one (3.7%) and three (10.7%) subjects in V5 and placebo arms, respectively had first-diagnosed, drug-sensitive TB; the remaining patients had re-treated TB, multidrug-resistant TB or HIV-TB coinfection. After 1 month, 26 out of 27 patients (96.3%) became sputum smear negative in the V5 group (p < 0.0000001), whereas seven out of 28 (25%) in the placebo group had converted (p = 0.005). V5 contributed to the downregulation of TB-associated inflammation, as shown by normalization of high leukocyte counts, erythrocyte sedimentation rate and faster defervescence than controls. Patients in both arms experienced an increase in the levels of hemoglobin corresponding to 128.9 ± 17.6 versus 133.1 ± 14.7 g/l (p = 0.03) and 112.6 ± 14 versus 117 ± 11.7 g/l (p = 0.03) in V5 and placebo arms, respectively. In total, 19 out of 28 placebo patients (67.9%) gained, on average, 1.07 kg (59.1 ± 10 vs 60.1 ± 10.4 kg; p = 0.003). By contrast, all patients in the V5 group gained weight with mean 3.4 kg (59.7 ± 8 vs 63.1 ± 9 kg; p = 5.7E-007). Clinical symptoms improved among all patients in V5 arm, while 28.6% of patients on placebo reported satisfactory results (p = 0.007). No adverse or side effects attributable to V5 were seen at any time. Further studies are needed to gauge the extent of the benefits of V5 as safe and effective adjunct immunotherapy for TB.