Foralumab is a human anti-CD3 monoclonal antibody being developed for the treatment of autoimmune and inflammatory diseases. The goal of this Phase 2a, randomized, double-blind placebo-controlled, multicenter dose-ranging study is to evaluate the use of nasal foralumab in patients with non-active secondary progressive multiple sclerosis (SPMS). The primary objectives that this study aims to answer are: 1. To determine the safety and tolerability of 50 μg/dose and 100 μg/dose of foralumab nasal compared to placebo 2. To investigate the effect of foralumab relative to placebo on the change from baseline \[18F\]PBR06-positron emission tomography (PET) scans for microglial activation, after 12 weeks (3) months of study treatment.
Multiple sclerosis (MS) is a common autoimmune disorder affecting young adults, driven by an aberrant T cell response against central nervous system (CNS) antigens. Epidemiologic studies show that approximately 50% of patients are classified as having relapsing-remitting multiple sclerosis (RRMS), while about 35% have SPMS and the remaining 15% have primary progressive MS (PPMS). Foralumab is a human anti-CD3 monoclonal antibody being developed for the treatment of autoimmune and inflammatory diseases. It is hypothsized that nasal foralumab will slow disability accumulation and microglial activation measured by PET imaging in non-active SPMS. This study is a randomized, double-blind, placebo-controlled, multicenter, parallel-group study of 2 doses of nasal foralumab (50 μg/dose or 100 μg/dose of foralumab nasal) compared to placebo in the treatment of non-active SPMS for 3 months (4 three-week cycles of treatment). Fifty-four subjects with non-active SPMS will be randomized 1:1:1 to one of three treatment cohorts: 1. Group A: Nasal foralumab 50 μg 3 days a week (Monday-Wednesday-Friday) for two weeks, followed by a one-week rest, comprising a 3-week cycle, for a total of four cycles. 2. Group B: Nasal foralumab 100 μg 3 days a week (Monday-Wednesday-Friday) for two weeks, followed by a one-week rest, comprising a 3-week cycle, for a total of four cycles. 3. Group C: Nasal placebo (acetate buffer) 3 days a week (Monday-Wednesday-Friday) for two weeks, followed by a one-week rest, comprising a 3-week cycle, for a total of four cycles.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
54
Foralumab nasal solution is a preservative-free, sterile, clear, colorless-to-slightly-yellow solution filled in an Aptar Unidose nasal atomizer device. Each Unidose device contains 0.13 mL foralumab placebo nasal solution, sufficient for administration to a single nare. Two Aptar Unidose devices will be used for a single dose (one device per nare). Each Unidose device contains foralumab nasal solution, supplied at either 25 μg foralumab or 50 μg foralumab, sufficient for administration into a single nare.
Foralumab placebo nasal solution is a preservative-free, sterile, clear, colorless-to-slightly-yellow solution filled in an Aptar Unidose nasal atomizer device. Each Unidose device contains 0.13 mL foralumab placebo nasal solution, sufficient for administration to a single nare. Two Aptar Unidose devices will be used for a single dose (one device per nare).
Yale
North Haven, Connecticut, United States
RECRUITINGJohns Hopkins
Baltimore, Maryland, United States
RECRUITINGBrigham and Women's Hospital
Boston, Massachusetts, United States
RECRUITINGUniversity of Massachusetts
Worcester, Massachusetts, United States
RECRUITINGUniversity of Buffalo
Buffalo, New York, United States
RECRUITINGCornell Weill Medical Center
New York, New York, United States
RECRUITINGThomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States
RECRUITINGThe number of patients with adverse event (AE) reports.
Time frame: Throughout the study, an average of 12 weeks (3 months).
Changes in the Total Nasal Symptom Score (TNSS).
The TNSS is the sum of scores over 24 hours and 2 weeks for nasal congestion, runny nose, nasal itching, sneezing, and difficulty sleeping. The TNSS is quantified using the following scale: None 0, Mild 1 (symptom clearly present but easily tolerated), Moderate 2 (symptom bothersome but tolerable), Severe 3 (symptom difficult to tolerate - interferes with activities).
Time frame: TNSS is performed during the Screening Visit and during the Treatment Period at the first visit of Cycle 1, Cycle 2, Cycle 3, and Cycle 4 (each Cycle is 3 weeks).
Change from baseline for [18F]PBR06-positron emission tomography (PET) scans for microglial activation after 12 weeks (3 months) of study treatment.
Subjects at all sites will undergo PET imaging with the radiotracer \[18F\]PBR06.
Time frame: Subjects will undergo PET imaging prior to Week 1 (i.e., prior to dosing) and after Week 12 (after Cycle 4 at the PET sub-study site).
Changes in the Expanded Disability Status Scale (EDSS).
The EDSS is a way of measuring changes in the level of someone's disability over time. The EDSS scale ranges from 0 to 10. Scores are in half unit steps with increasing scores indicating worsening and decreasing scores indicating improvement.
Time frame: EDSS is performed during the Screening Visit and during the Treatment Period at the first visit of Cycle 1, Cycle 2, Cycle 3, and Cycle 4 (each Cycle is 3 weeks).
Changes in the Multiple Sclerosis Functional Composite-4 (MSFC-4).
The MSFC-4 is the average of the timed 25-foot walk (T25FW), the nine-hole peg test for the dominant hand (9HPT-D), symbol digit modality test (SDMT), and low contrast visual acuity (LCVA) scores.
Time frame: MSFC-4 is performed during the Screening Visit and during the Treatment Period at the first visit of Cycle 1, Cycle 2, Cycle 3, and Cycle 4 (each Cycle is 3 weeks).
Changes in the Modified Fatigue Impact Scale (MFIS).
The full-length MFIS consists of 21 items with each question specifying a range of impact from 0 (Never) to 4 (Almost always). The total score for the MFIS is the sum of the scores for the 21 items.
Time frame: MFIS is performed during the Screening Visit and during the Treatment Period at the first visit of Cycle 1, Cycle 2, Cycle 3, and Cycle 4 (each Cycle is 3 weeks).
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.