A Study to Evaluate Efficacy, Safety, and Tolerability of Alemtuzumab in Pediatric Patients With RRMS With Disease Activity on Prior DMT

Number of participants with at least one new or enlarged T2 lesions was reported in this outcome measure. Number of new or enlarged T2 lesions was defined as the total number of new or enlarged T2 lesion that occurred during the study divided by the total number of follow-up months until the end of each period.

EDSS was an ordinal scale in half-point increments that qualified disability in participants with MS. It consisted of 8 ordinal rating scales assessing seven functional systems (FS) (pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral, and other). Ambulation scoring was done to conclude evaluation. EDSS steps 1.0 to 4.5 referred to participants with MS who were fully ambulatory, while EDSS steps 5.0 to 9.5 were defined by the impairment to ambulation. Individual FS scores were then used in conjugation with ambulation score to obtain total EDSS score which ranged from 0 (normal neurological examination) to 10 (death due to MS) in half-point increments, where higher scores indicated worst outcomes. Baseline for EDSS was defined as the last non-missing value prior to the first course of alemtuzumab.

Adjusted ARR was defined as the total number of relapses that occurred during the alemtuzumab treatment phase divided by the total number of follow-up years and was estimated based on negative binomial regression. Relapses were defined as new or recurrent neurological symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the neurologist and documented by the functional system scores.

BVMT-R: tool to measure visuospatial learning and memory abilities across research and clinical settings. Visual display of 6 simple figures arranged in 2x3 matrix on separate pages was shown to participants for 3 consecutive 10-second trials. After each trial, participants drew as many designs as accurately as they could in correct location. They were asked to reproduce designs in exact layout after 25-minute delay filled with other distractor tasks. Forced-choice recognition trial was administered immediately after delayed memory trial. Optional copy trial was included at end of test where participants were asked to copy figure display accurately. Scoring of immediate, delayed recall and copy trials were based on accuracy of drawings and location of figures. Score range 0 to 12 per trial; total score: 0 to 36 for all 3 trials. Higher scores: better visuospatial memory. Change from baseline in total score is presented. Baseline:Month -4 for Period 1;Month 4 for Period 2.

The SDMT was used to assess cognitive impairment and involved a simple substitution task that normal children and adults could easily perform. Using a reference key, the examinee/participant had 90 seconds to pair specific numbers with given geometric figures. Responses were only in oral form for this study and administration time was just 5 minutes. The number of corrected substitutions and number of completed responses were recorded. The score for each was the number of correctly coded items ranging 0-110 in 90 seconds; higher scores indicated a better outcome. Change from baseline in number of completed responses and number of corrected substitutions by SDMT is presented. Baseline: Month -4 for Period 1; Month 4 for Period 2.

The PedsQL™ measurement model was a modular approach to measure health-related quality of life (HRQOL) in healthy children and adolescents and those with acute and chronic health conditions. It included a child and teen self-report, and parents' report of children and teen. Each report consisted of 23 items and 4 scales (physical, emotional, social and school functioning). Each item used a 5-point rating scale (from 0='it is never a problem' to 4='it is almost always a problem'). Items are reverse scored and linearly transformed to a 0 (almost always) to 100 (never) scale. Total scores (0 to 100) for each report were mean of specific items where higher score indicated better HRQoL. Baseline: last non-missing value prior to first course of alemtuzumab.

Pediatric NeuroQoL was measurement system that evaluated and monitored physical, mental and social effects experienced by children living with neurological conditions. Physical effects (fatigue, pain) and mental effects (cognitive function, anxiety, depression) was assessed. Each domain had 8 to 10 items and participants indicated how often they experienced feelings and circumstances related to each domain on scale 1 to 5 (1='never' to 5='almost always'). This scale was reversed for cognitive function (1='very much' to 5='not at all'). Higher values: worse outcome for fatigue, pain, anxiety, depression, and better cognitive function. Raw scores were re-scaled to standardized scores with mean=50 and standard deviation=10. T-score range: 20 to 80. T-score <30 indicated clinically significant impairment. Change from baseline in physical and mental effects scores by pediatric NeuroQoL is presented. Baseline: last non-missing value prior to first course of alemtuzumab.

Blood samples were collected at the specified timepoints for measurement of serum concentrations of alemtuzumab.

Blood samples were collected at the specified timepoints for determination of Cmax of alemtuzumab.

Blood samples were collected at the specified timepoints for determination of Tmax of alemtuzumab.

Blood samples were collected at the specified timepoints for determination of AUC of alemtuzumab.

Blood samples for full PK analysis were collected at the specified timepoints for determination of AUC0-last of alemtuzumab.

Blood samples were collected at the specified timepoints for determination of T1/2z of alemtuzumab.

Blood samples were collected for assessment of lymphocytes (CD19, CD3, CD3-/16+56, CD4 and CD8). Baseline was defined as the last non-missing value prior to first course of alemtuzumab.

Blood samples were collected for assessment of lymphocytes (CD4 and CD8). Baseline was defined as the last non-missing value prior to first course of alemtuzumab. Change from baseline in CD4/CD8 ratio is presented.

An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which did not necessarily have a causal relationship with study treatment. A serious AE (SAE) was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was a medically important event. An AESI was an AE (serious or non-serious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required.

An IAR was defined as any AE that occurred during alemtuzumab infusion or within the 24 hour post-infusion period. Number of participants with IARs in the alemtuzumab treatment phase is presented.

Blood samples were collected to evaluate antibodies to alemtuzumab. Percentage of participants with positive ADA sample status are reported. Percentages are rounded off to tenth decimal place.