Table 2.
Published Phase I-III studies on the human-attenuated rotavirus vaccine RIX4414
| Product | Phase | Principal aim | No. of subjects/RV serotypes | Most relevant results |
|---|---|---|---|---|
| 89-12 105 pfu | I | Safety and immunogenicity in adults, and in rotavirus-seropositive children and infants. Placebo-controlled | 34 adults; 40 positive 2-12-year-old children; 9 and 42 infants 6-26 weeks receiving 1 and 2 doses, respectively. | Proof of concept: Acceptable tolerance and safety; high vaccine shedding; high IgA seroconversion |
| 89-12 105 pfu | II | Safety, immunogenicity, and efficacy of two doses in infants. Placebo-controlled | 215 healthy infants 10-16 weeks of age/G1 rotavirus season | Fever >38.1°C only significant side effect; 95% seroresponse; 89/78% efficacy against all/severe RVGE |
| 89-12 105 pfu | II | Second year follow-up of previous study | 184 infants available for follow-up/G1 rotavirus season | 59-90% efficacy against all/severe RVGE for year 2 |
| RIX4414 104.7-106.4 ffu | I | Similar to Phase I study. Includes evaluation of doses and of a buffer for vaccine dilution. Finnish children; placebo-controlled | 33 adults, 26 positive 1-3-year-old toddlers; 192 infants divided into 4 groups | No significant side effect; 73-96% seroconversion and 38-60% shedding by ELISA both increasing with increasing doses; catch-up, but no booster effect with second dose |
| RIX4414 105.2 and 106.4 ffu | II | Safety, immunogenicity, vaccine shedding, and effect of breastfeeding and other coadministered vaccines. Placebo-controlled | 529 infants divided into 3 groups received either the lower or the higher concentration or placebo in a 2:2:1 randomization | No significant side effects; 81-88% vaccine take in lower/higher concentration and 54-58% vaccine shedding by ELISA. 10-12% reduced take with breastfeeding |
| RIX4414 104.7 ffu | II | Efficacy of two doses after a first and a second rotavirus season. Placebo-controlled | 405 infants 6-12 weeks of age/G1 predominant season | No significant side effects; 73-90% efficacy against all/severe RVCE year 1; 73-83% and 72-85% for entire follow-up period (1.4 years) |
| RIX4414 104.7-105.8 ffu | IIb | Efficacy, safety, and immunogenicity of two doses at three concentrations in Latin American children. Placebo-controlled | 2155 infants 6-12 weeks of age (~540 per group). Subset studied for immunogenicity/G1 and G9 predominant season | No significant side effects; up to 60% seroconversion; 35-44% shedding post dose one; no immune competition with DTP-Hep B-Hib (oral polio differed); 56-70% and 66-086% efficacy against any and severe RVGE, respectively, with increased efficacy at higher dose. Protection demonstrated against G1 and G9 serotypes |
| RIX4414 104.7-106.1 ffu | IIb | Efficacy, safety, and immunogenicity of two doses at three concentrations in Singaporean children. Placebo- controlled | 2464 infants 11-17 weeks of age (~650 per group except for 510 in lower dose). Subset studied for immunogenicity. Serotypes could not be determined owing to low number of RVGE cases | No significant side effects; up to 91% seroconversion; 76-80% shedding post dose one; 3 cases of vaccine virus transmission; no immune competition with DTP-Hib-IPV. Efficacy could not be evaluated |
| RIX4414 106.5 median cell- culture infective doses* | III | Safety with a primary focus on IS. Efficacy against overall severe RVGE, hospitalization and ≠ circulating types, mostly in Latin American children | 63,225 infants, 6-13 months of age were enrolled and followed-up to 6 months for safety of whom 20,169 were enrolled for efficacy up to 12 months of age | IS 1.89 vs 2.21/104 in vaccinees vs placebo; 85% efficacy against severe RVGE and hospitalization; 40-42% efficacy against any severe GE/any GE hospitalizations; high protection for G1, G3, G9, and a protective trend for G2; not enough cases for G4 |
*Similar to 106 ffu, RVGE = Rotavirus gastroenteritis, DTP-HepB-Hib = Diphtheria-tetanus-pertussis, hepatitis B and Haemophilus influenzae type B vaccine, DTP-Hib-IPV = Diphtheria-tetanus-pertussis, Haemophilus influenzae type B and inactivated polio vaccine, ELISA = Enzyme-linked immunosorbent assay, ffu = focus-forming unit, GE = Gastroenteritis, Ig = Immunoglobulin, IS = Intussusception, pfu = plaque-forming unit, RVGE = Rotavirus gastroenteritis