ATX-MS-1467 in Multiple Sclerosis

The number of T1 CELs were measured using MRI scans.

T1 CELs were measured using MRI scans. Baseline was calculated as the average number of T1 CELs during the 3 visits in the Baseline Control Period (Weeks -8, -4 and 0).

T1 CELs were measured using MRI scans. Baseline was calculated as the average number of T1 CELs during the 3 visits in the Baseline Control Period (Weeks -8, -4 and 0).

T2 lesions were measured using MRI scans.

T1 CELs were measured using MRI scans.

T1 CELs were measured using MRI scans.

Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. These new or worsening symptoms should be noted by the subject and must be accompanied by at least one of the following: An increase of greater than or equal to (>=) 1 grade in >=2 functional scales of the Expanded Disability Status Scale (EDSS) or an increase of >=2 grades in 1 functional scale of the EDSS or an increase of >= 0.5 or an increase of >=1.0 in EDSS if the previous EDSS was 0. Annualized Relapse Rate was calculated as = 365.25 x (Number of relapses during Treatment Period) per (Number of days on treatment during Treatment Period).

Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. These new or worsening symptoms should be noted by the subject and must be accompanied by at least one of the following: An increase of greater than or equal to (>=) 1 grade in >=2 functional scales of the Expanded Disability Status Scale (EDSS) or an increase of >=2 grades in 1 functional scale of the EDSS or an increase of >= 0.5 or an increase of >=1.0 in EDSS if the previous EDSS was 0. Time to first relapse was defined as the time in days from the date of first dose of study treatment to the date of first multiple sclerosis relapse.

EDSS is an ordinal scale in half-point increments that qualifies disability in subjects with Multiple Sclerosis. It consists of 8 ordinal rating scales assessing seven functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as any other neurological findings due to Multiple Sclerosis. Total EDSS score ranges from 0 (normal neurological examination) to 10 (death due to MS). Baseline was defined as the last measurement taken prior to the first dose of study drug (Week 0).

The MSFC is a multidimensional clinical outcome measure which consists of three sub-tests; Timed 25-Foot Walk, 9-Hole Peg Test and Paced Auditory Serial Addition Test-3(PASAT-3). The Timed 25-Foot Walk is a quantitative measure of lower extremity function. The 9-Hole Peg Test is a quantitative measure of upper extremity (arm and hand) function. The PASAT is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. Standardized results (Z-scores) of these sub-tests and the overall MSFC Z-score as an average of these three Z-scores was calculated. Higher Z-scores reflect better neurological function and a positive change from baseline indicates improvement. An increase in score indicates an improvement (range -3 to +3). Baseline was defined as the last measurement taken prior to the first dose of study drug (Week 0).

An adverse event (AE) was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the study drug. An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent adverse events are defined as any adverse event with a start date on or after the date of first dose and within 28 days after the date of last dose in the current study. TEAEs include both Serious TEAEs and non-serious TEAEs.

Treatment-emergent ISRs were defined as any ISR with a start date on or after the date of first dose and within 7 days after the date of last dose in the current study. Injection site reactions were identified as erythema, induration, pruritus, nodules and/or cysts, ecchymosis, pain and local edema.