DX64
A Phase II Double-Blind Placebo Cross-over Clinical in Secondary Progressive Multiple Sclerosis
Hyperimmune caprine serum (HICS) containing a stabilsed neuropeptide and its role in the treatment of SPMS
Objectives:
The objective of this phase II clinical trial was to determine whether HICS could elicit measurable efficacy in patients with SPMS.
Methods:
The phase II double-blind placebo controlled (DBPC) crossover clinical trial in 20 patients with MRI and clinically confirmed SPMS was undertaken with ethics approval in the UK. The mean age of the cohort was 50.3 yrs and M:F ratio of 1:4. The mean time since onset of MS symptoms was 18.7 yrs and since onset of SPMS was 5.7 yrs. 90% of patients used walking aids at enrolment. Patients were randomised and treated twice weekly with either 4.5mg/ml s.c. (1ml) of HICS or placebo for 4 weeks. Following a six week washout period the converse treatment was administered for 4 weeks (crossover). After 14 weeks, patients entered the open-label (OL) phase with twice weekly HICS administered up to 12 months.
Results:
HICS was safe and well-tolerated in all phases of the trial. No treatment related severe adverse events were recorded.
HICS did not show a significant difference in bladder function in the DBPC phase. Mean urinary frequency by visit for the OL phase showed that HICS significantly decreased the mean frequency, p<0.0001 and mean urinary incontinence, p=0.0009.
The mean total MSFC score in the DBPC phase showed HICS significantly increased the total MSFC score from (-0.259 to 0.177), p=0.0215. The mean total MSFC score by visit for the OL phase also suggested that a longer period of treatment with HICS significantly increased the total MSFC score at W52 (p=0.021).
25-foot walk showed that HICS significantly increased the mean score from baseline -1.346 to the end of the DBPC phase -0.586 (p=0.049) when compared against placebo treatment (p=0.338). HICS significantly increased the mean 9-HPT versus placebo in the DBPC phase (p=0.046). The PASAT 3 showed HICS treatment also significantly increased the mean score from baseline (0.462) to end of the DBPC phase (0.752), p=0.006. HICS significantly improved visual acuity (LogMar - eyes combined) in the DBPC phase (p=0.026).
HICS significantly decreased the mean MSIS physical scale in the DBPC phase, p=0.007 and significantly increased the overall I-QOL baseline, p=0.007 during the OL phase only. The mean change in EDSS score showed that HICS did not significantly decrease the EDSS during the DBPC or OL phases from baseline to W52, p=0.287.
Conclusions:
The Phase II DBPC trial was a proof of concept and safety trial, as part of the development of HICS. The medication was well tolerated with minor injection site reactions being the main side effect. The trial did not show improvement in several functional outcome measures. Observed improvement continued from the DBPC to OL phases. The results suggest that subjects treated over a longer treatment period may be expected to show greater levels of efficacy.