Only subjects that have completed TILS-021, a Phase 2a Randomized, Double-Blind, Placebo-Controlled, Multicenter Dose-Ranging Study of Nasal Foralumab in Non-Active Secondary Progressive Multiple Sclerosis Patients are eligible to be enrolled in TILS-022. TILS-022 is a 6-month open-label extension study with an opportunity for dose to be escalated based on the subject's clinical status. All subjects initiate dosing in this trial at a dose of nasal foralumab 50 µg 3 days a week (Monday, Wednesday, and Friday) for 2 weeks, followed by a 1-week rest, comprising a 3-week cycle. At week 12, the dose may be escalated to 100 µg according to pre-defined dose escalation rules. Study TILS-022 is intended to ensure all participants in TILS-021, a placebo-controlled study, will be able to receive open-label nasal foralumab for 6 months. The option to extend this trial for longer than 6 months will be explored with FDA by the Sponsor.
TILS-021 (NCT06292923) is an ongoing Phase II dose-ranging study, the dosing regimen imitates that employed in the nonclinical studies that is, Monday-Wednesday-Friday for two consecutive weeks and then one rest week. This is believed to optimize the immunologic response to anti-CD3. It will assess the safety and potential efficacy as reflected in microglial activation on the PET scan, neurologic exam and measures, and immunologic changes in response to nasal foralumab administration in a randomized, double-blind, placebo-controlled, multicenter Phase II study of non-active secondary progressive MS patients with three months of treatment. Patients completing TILS-021will be eligible to enroll in study TILS-022. The primary objectives of this study in subjects with non-active secondary progressive multiple sclerosis (SPMS) that have successfully completed study TILS-022 are to evaluate 6-month (Day 169) safety data of nasal foralumab, as assessed by adverse event reports; changes in laboratory values; changes in physical, neurological, or nasal examinations; or changes in Total Nasal Symptom Score (TNSS). Objective 2 is to assess the clinical effect of foralumab after 6 months (Day 169) of treatment relative to baseline, as measured by the Modified Fatigue Impact Scale (MFIS).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
55
Patients meeting the requirements of the dose escalation rules will receive nasal foralumab 100 µg three (3) days a week (Monday-Wednesday-Friday) for two weeks, followed by a one-week rest, comprising 3-week cycles.
Brigham and Women's Hospital
Boston, Massachusetts, United States
RECRUITINGSafety and Tolerability
The safety and tolerability of 50 µg/dose and 100 µg/doses of foralumab nasal as measured by adverse event reports
Time frame: Day 1 vs Day 169 (end of study)
Change in Baseline
Assess change in baseline Modified Fatigue Impact Scale (MFIS) Scores range from 0-84. 0 is the minimum score and 84 is the maximum score. Lower scores indicate less fatigue while higher scores indicate increased fatigue.
Time frame: Day 1 vs Day 169 (or termination)
Safety and Tolerability
Blood pressure will be monitored at the beginning of every cycle. Increases and decreases in baseline will be monitored assessed for safety.
Time frame: Day 1 vs Day 169 (or termination)
Safety and Tolerability
Heart rate will be monitored at the beginning of every cycle. Increases and decreases in baseline will be monitored assessed for safety.
Time frame: Day 1 vs Day 169 (or termination)]
Safety and Tolerability
Lab values such as CHEM7 and CBC will be monitored at the beginning of every cycle on day 1. Any increases or decreases in baseline lab values will be assessed for safety.
Time frame: Day 1 vs Day 169 (or termination)
Safety and Tolerability
Total Nasal Symptom Score (TNSS). Scores range from 0-3 where 0 (minimum score) is no symptoms and 3 (maximum score) is severe. Higher scores indicate worse outcome.
Time frame: Day 1 vs Day 169 (or termination)
Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue
Assess change in baseline PROMIS Fatigue Short Form 7a. Scores range from 0-35 where the lower number indicated less fatigue.
Time frame: Day 1 of study vs End of Study (Day 169) or Early Termination
Baseline Neurostatus Expanded Disability Status Scale (EDSS)
Assess change in baseline Neurostatus EDSS. Scores range from 0-10 where the lower number indicates less disability.
Time frame: Day 1 of study vs End of Study (Day 169) or Early Termination.
Baseline Multiple Sclerosis Functional Composite (MSFC-4)
Assess change in baseline Multiple Sclerosis functional composite (MSFC-4)
Time frame: Day 1 of study vs End of Study (Day 169) or Early Termination
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