Daclizumab high-yield process in relapsing- remitting multiple sclerosis(SELECT): a randomised, double-blind, placebocontrolled trial

Ralf Gold, Gavin Giovannoni, Krzysztof selmaj, Eva Havdova, Xavier Montalban, Ernst- Wilhelm Radue .etal
The Lancet Vol 381June 22, 2013

Interleukin-2 signalling has a central role in the activation and regulation of the human immune system. Increased expression of the subunit (CD25) of the IL-2 receptor on nave T cells heightens the risk for Multiple Sclerosis. Daclizumab is a humanised monoclonal antibody specific for CD25. CD25 antagonism causes an expansion of immunoregulatory CD56 natural killer cells, inhibition of T- cell activation by dendritic cells and a reduction in lymphoid tissue inducer cells.

These immunological effects are reported to its therapeutic effects in multiple sclerosis. Daclizumab high-yield process(HYP) has the same aminoacid sequence as previous Daclizumab but differs in its glycosylation profile.

Assessing the effectiveness of Daclizumab HYP as monotherapy for an extended treatment period in patients with relapsing-remitting multiple sclerosis.

Study type: Randomized, Double blind, placebo controlled, multicentric Study period: Feb15, 2008-May14, 2009 Sample size: 621 patients Primary outcome measure: mortality Secondary outcome measure:

Age of patients: 18-55 yrs They had relapsing-remitting multiple sclerosis, according to McDonald criteria. They had a baseline Expanded Disability status scale (EDSS) score of 5.0 or less. They had atleast one confirmed multiple sclerosis relapse in the 12 months before randomisation, or atleast one gadolinium enhancing lesion on brain MRI

Primary-progressive, secondary-progressive, or progressive-relapsing multiple sclerosis.

739 pts. were screened for eligibility, out of which 621 pts. were randomised. Pts. Were randomly assigned in a 1:1:1 ratio to receive either Daclizumab HYP 150mg or 300mg, or placebo, subcutaneously once in every 4wks for 52wks. Primary endpoint was annualised relapse rate at wk52.Relapses were defined as new or recurrent neurological symptoms lasting 24hrs or more, accompanied by new neurological findings

Secondary endpoints were the cumulative number of new gadolinium-enhancing lesions on brain MRI scans done at wks 8,12,16, 20 and 24 wks; the no. of new enlarging T2 hyperintense lesions at wk52;the proportion of relapsing pts.btw baseline & wk52, quality of life. Tertiary end point were confirmed disability progression, as measured by change in EDSS score btw baseline & wk52, health related quality of life endpoints were patients global assessment of wellbeing , assessed by the EuroQoL visual analogue scale

Figure 2 shows the trial profile. As shown in Table1,demographic and baseline disease characteristics were similar btw 3 gps. ARR at 52 wks was lower in the Daclizumab HYP gp. Pts. than placebo gp. as seen in table 2 and fig.3 Longitudinal analysis showed that gadoliniumenhanced lesion activity was greater in the 150mg gp. than in 300mg gp during wks 4-24, but was similar at wk 52( figure 4)