Safety, Tolerability, Efficacy, and Pharmacokinetics of JBT-101 in Systemic Sclerosis

CRISS components included the following domains: modified Rodnan skin score, forced vital capacity percent predicted, Physician Global Assessment, Patient Global Assessment, and Health Assessment Questionnaire Disability-Index. An algorithm determines the predicted probability of improvement from baseline by incorporating change in the mRSS, FVC percent predicted, Physician and Patient Global Assessments, and HAQ-DI. The outcome is a continuous variable between 0.0 and 1.0 (0 - 100%). A cut-off at 0.6 in the predicted probability of being improved has yielded the smallest misclassification error. Subjects are not considered improved if, between Visit 1 and 6, they develop new: 1) renal crisis; 2) decline in FVC% predicted by 15% (relative) from baseline and confirmed after 1 month; or 3) left ventricular failure (systolic ejection fraction \< 45%) or pulmonary artery hypertension. Higher CRISS scores indicates improvement.

Time frame: Day 85 and Day 113

Population: Per the statistical analysis plan, the intent was to analyze all subjects receiving lenabasum and compare to those subjects receiving placebo for this endpoint. As such, individual lenabasum groups were not reported to follow the pre-specified statistical analysis plan. Only subjects with values at Visit 5 and 6 were included in this analysis.

The overall number of subjects with TEAE's per treatment group during active dosing (Days 1-84) plus the 28 day follow-up.

Time frame: Part A: Day 113

Population: Per the statistical analysis plan, the intent was to analyze all subjects receiving lenabasum and compare to those subjects receiving placebo for the primary endpoint. As such, individual lenabasum groups were not reported to follow the pre-specified statistical analysis plan.

The LS mean change from baseline (CFB) at Visit 5 (Day 85) and 6 (Day 113) is provided for FVC percent predicted. Change from Baseline was calculated as Visit 5 - Baseline and independently Visit 6 - Baseline.

Time frame: Day 85 and 113

Change from Baseline was calculated as Visit 5 - Baseline and independently Visit 6 - Baseline. Health Assessment Questionnaire - Disability Index includes 8 sections: dressing, arising, eating, walking, hygiene, reach, grip, and activities. There are two or three questions for each section. Scoring within each section is from 0 (without any difficulty) to 3 (unable to do). The eight scores of the eight sections are summed and divided by 8. If one section is not completed by a subject, the summed score is divided by 7. As such, maximum scores can vary with a min of 0. The result is the DI, the disability index or functional disability index. Higher scores indicate worse symptomology

Time frame: Day 85 and 113

The LS mean change from baseline (CFB) at Visit 5 (Day 85) and 6 (Day 113) is provided for patient global assessment. Change from Baseline was calculated as Visit 5 - Baseline and independently Visit 6 - Baseline. The assessment at each specified visit will be performed with a segmented numerical version of the visual analogue scale in which the subject selects a whole number (0-10 integers) that best reflects the overall disease activity. The numerical rating score is anchored by two verbal descriptors, one of no disease activity (score of 0) and one of worse imaginable disease activity (score of 10), with numbers 1-9 spaced equidistance in between. The subject will select an integer to describe disease activity. The recall period is one week.

Time frame: Day 85 and 113

The LS mean change from baseline (CFB) at Visit 5 (Day 85) and 6 (Day 113) is provided for physician global assessment. Change from Baseline was calculated as Visit 5 - Baseline and independently Visit 6 - Baseline. The Physician Global Assessment of disease activity will be performed using a segmented numerical version of the visual analogue scale in which the physician selects a whole number (0-10 integers) that best reflects the overall disease activity. The numerical rating score is anchored by 2 verbal descriptors, one of no disease activity (score of 0) and one of worse imaginable disease activity (score of 10), with numbers 1-9 spaced equidistance in between. The physician will select an integer to describe disease activity. The recall period is one week.

Time frame: Day 85 and 113

The LS mean change from baseline (CFB) at Visit 5 (Day 85) and 6 (Day 113) is provided for mRSS total score. Change from Change from Baseline was calculated as Visit 5 - Baseline and independently Visit 6 - Baseline. The mRSS consists of an evaluation of patient's skin thickness rated by clinical palpation using a 0-3 scale (0 = normal skin; 1 = mild thickness; 2 = moderate thickness; 3 = severe thickness with inability to pinch the skin into a fold for each of 17 surface anatomic areas of the body: face, anterior chest, abdomen, and, with right and left sides of the body separately evaluated, the fingers, forearms, upper arms, thighs, lower legs, dorsum of hands and feet. Individual values are summed and defined as the total skin score. Total score is 0 to 51 with higher scores indicating worse symptomology

Time frame: Day 85 and 113