daclizumab high-yield process in relapsing- remitting multiple sclerosis(select

7/27/2019 Daclizumab High-yield Process in Relapsing- Remitting Multiple Sclerosis(SELECT

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Daclizumab high-yield process inrelapsing- remitting multiple

sclerosis(SELECT):a randomised, double-blind, placebo-

controlled trialRalf Gold, Gavin Giovannoni, Krzysztofselmaj, Eva Havdova, Xavier Montalban,

Ernst- Wilhelm Radue .etal

The Lancet Vol 381June 22, 2013


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Interleukin-2 signalling has a central role in the

activation and regulation of the human immunesystem.

Increased expression of the subunit (CD25) of

the IL-2 receptor on nave T cells heightens therisk for Multiple Sclerosis.

Daclizumab is a humanised monoclonal antibodyspecific for CD25.

CD25 antagonism causes an expansion ofimmunoregulatory CD56 natural killer cells,inhibition of T- cell activation by dendritic cells

and a reduction in lymphoid tissue inducer cells.


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These immunological effects are reported to its

therapeutic effects in multiple sclerosis.Daclizumab high-yield process(HYP) has the sameaminoacid sequence as previous Daclizumab butdiffers in its glycosylation profile.


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Assessing the effectiveness of Daclizumab HYP

as monotherapy for an extended treatmentperiod in patients with relapsing-remittingmultiple sclerosis.


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Study type: Randomized, Double blind, placebocontrolled, multicentric

Study period: Feb15, 2008-May14, 2009

Sample size: 621 patients

Primary outcome measure: mortality

Secondary outcome measure:


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Age of patients: 18-55 yrsThey had relapsing-remitting multiple sclerosis,according to McDonald criteria.

They had a baseline Expanded Disability statusscale (EDSS) score of 5.0 or less.

They had atleast one confirmed multiplesclerosis relapse in the 12 months beforerandomisation, or atleast one gadoliniumenhancing lesion on brain MRI


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Primary-progressive, secondary-progressive, or

progressive-relapsing multiple sclerosis.


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739 pts. were screened for eligibility, out of which

621 pts. were randomised.

Pts. Were randomly assigned in a 1:1:1 ratio toreceive either Daclizumab HYP 150mg or 300mg,

or placebo, subcutaneously once in every 4wks for52wks.

Primary endpoint was annualised relapse rate atwk52.Relapses were defined as new or recurrent

neurological symptoms lasting 24hrs or more,accompanied by new neurological findings


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Secondary endpoints were the cumulative number

of new gadolinium-enhancing lesions on brain MRIscans 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 scorebtw baseline & wk52, health related quality of lifeendpoints were patients global assessment ofwellbeing , assessed by the EuroQoL visual

analogue scale


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Figure 2 shows the trial profile.

As shown in Table1,demographic and baselinedisease 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 andfig.3

Longitudinal analysis showed that gadolinium-enhanced lesion activity was greater in the 150mggp. than in 300mg gp during wks 4-24, but wassimilar at wk 52( figure 4)

daclizumab high-yield process in relapsing- remitting multiple sclerosis(select

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