Table 3.
Incidence of binding and neutralizing antibodies to romiplostim and thrombopoietin in placebo-dosed subjects
| Study description | Total subjects | Treatment regimen | Antibody assessment time-points | Number of subjects with pre-existing antibody to romiplostima (n, incidence, %) | Number of subjects with pre-existing antibody to thrombopoetina (n, incidence, %) | Number of subjects with neutralizing antibody response to thrombopoetin (n, incidence, %) | Neutralizing antibody response to romiplostim/TPO (n, incidence, %) |
|---|---|---|---|---|---|---|---|
| Phase 2, multicenter, randomized, dose-finding, placebo-controlled study evaluating safety, PK/PD, and efficacy of romiplostim in thrombocytopenic subjects with ITP | 4 | SC doses of romiplostim at 0.2, 0.5, 1.0, 3.0, 6.0, or 10 µg/kg; subjects in each dose cohort received second dose at day 15 or day 22 if platelet counts were <50 × 109/L | Pre-dose, week 4 and week 11 | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Pivotal, phase 3, randomized, double-blind, placebo-controlled, 24-week study to assess efficacy (platelet response) and safety in treating adult thrombocytopenic subjects with ITP who have not yet undergone splenectomy | 21 | 1 to 15 µg/kg SC; weekly dosing, adjusted on the basis of platelet counts for 24 weeks | Pre-dose, week 9, week 17, and week 24 (end of study) | 2 (10) | 2 (10) | 0 (0) | 0 (0) |
| Pivotal, phase 3, randomized, double-blind, placebo-controlled, 24-week study to assess efficacy (durable platelet response) and safety in treating adult thrombocytopenic subjects with ITP refractory to splenectomy | 20 | 1 to 15 µg/kg SC; weekly dosing, adjusted on the basis of platelet counts µg/kg), for 24 weeks | Pre-dose, week 9, week 17, and week 24 (end of study) | 2 (10) | 4 (20) | 0 (0) | 0 (0) |
| Total (sum of all studies)b | 45c | 4 (9) | 6 (13) | 0 (0) | 0 (0) |
Serum samples from placebo-controlled arm of one Phase 1 dose-finding study and two Phase 3 studies were evaluated for antibodies to romiplostim and TPO. Incidence of antibodies was expressed as a percentage and derived from number of subjects positive for anti-romiplostim or TPO/total number of subjects for a particular study.
aPlacebo subjects were considered positive for pre-existing antibodies if they were positive at the pre-dose or post-dose time-point.
bTotal incidence was expressed as a percentage and derived from number of subjects positive for the relevant anti-romiplostim or anti-TPO antibody/total number of subjects enrolled.
cOf the 45 subjects in the placebo-dosed group, 35 subjects rolled over into the ongoing long-term extension study and were dosed for the first time in this study. Hence, only ten placebo-dosed subjects remained at the time of analysis.