Objective

To summarize the safety and efficacy results from the multi-centre repeat treatment open-label (OL) extension trial (Study 147). The following summary is based on both published⁶³ and unpublished data.⁵¹

Trial Description

Ambulatory (Gross Motor Function Classification System levels I to III) pediatric patients (aged 2 to 17 years of age) with cerebral palsy (CP) and dynamic equinus foot deformity who had completed the double-blind portion of Study 141 (patients had to have had at least 12 weeks of follow-up post-injection) and who had no ongoing adverse events could enrol into the OL extension study. A maximum of four treatments of abobotulinumtoxinA (aboBoNTA) of 5 U/kg to 30 U/kg occurring at 12-week intervals were administered in the OL extension, with the first one occurring at or after the week 12 visit of the double-blind study. (However, the visit could be postponed until weeks 16, 22, 28, or later according to the investigator’s judgment.) The OL extension lasted for a total of 12 months (40 weeks post–treatment cycle 1; 28 weeks post–treatment cycle 2; 16 weeks post–treatment cycle 3, or four weeks post–treatment cycle 4). The primary objective of the OL extension study was to assess the long-term safety (assessed as adverse events and serious adverse events) of repeated aboBoNTA treatments for lower-limb spasticity (LLS) in CP patients. The secondary objective was to assess the efficacy of repeated aboBoNTA treatments using the Modified Ashworth Scale (MAS) at the ankle joint, the Physician’s Global Assessment (PGA) of treatment response, goal attainment scaling (GAS), the Tardieu Scale (TS), the Observational Gait Scale (OGS), lower-limb pain, duration of effects, time intervals between–treatment, and quality of life. Both safety and efficacy were analyzed descriptively with no formal statistical significance analyses planned. It should be noted, however, that the dosing in the two aboBoNTA groups included a range of dosing, with ranges of 7.5 U/kg to 12.5 U/kg in the aboBoNTA 10 U/kg group, and 12.5 U/kg to 17.5 U/kg in the aboBoNTA 15 U/kg group.

Results

Critical Appraisal

The main limitations of the extension phase were the OL nature of the study (which can potentially bias the reporting of the outcome measure, especially the subjective measures), the lack of a control group, the limited sample size of what is likely a highly select population (due to a large number of patients not continuing therapy in treatment cycles 2, 3, and 4), the fact that the aboBoNTA 10 U/kg group included dosing that ranged anywhere from 7.5 U/kg to 12.5 U/kg and the aboBoNTA 15 U/kg group included dosing ranging from 12.5 U/kg to 17.5 U/kg, and the fact that the aboBoNTA 10 U/kg group also included those patients initially in the placebo arm of the double-blind portion of the original study. These limitations preclude the ability to draw meaningful conclusions with regard to the efficacy of aboBoNTA 10 U/kg or aboBoNTA 15 U/kg. However, the main purpose of the extension study was to provide a long-term safety assessment of the two aboBoNTA doses. There were no new safety signals identified in the extension trials.

Summary

The OL extension study reported data from patients who continued to receive up to four treatment cycles of aboBoNTA 10 U/kg (which included patients originally randomized to the placebo group in the double-blind study and switched over, and which also included a range of aboBoNTA dosing of between 7.5 U/kg and 12.5 U/kg) or aboBoNTA 15 U/kg (which also included a range of aboBoNTA dosing of between 12.5 U/kg and 17.5 U/kg). No new safety signals were evident, with the most common adverse events being nasopharyngitis, pharyngitis, and upper respiratory tract infection. Very little can be concluded regarding the efficacy of aboBoNTA due to the aforementioned limitations associated with the OL extension phase. Therefore, no definitive conclusions can be made regarding the long-term treatment of aboBoNTA.