A Study of Nasal Foralumab in Non-Active Secondary Progressive Multiple Sclerosis Patients

NCT06292923 | Recruiting Phase 2 FDA Drug

• 1 other identifier: TILS-021
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 7

Brief Summary

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. 1.To determine the safety and tolerability of 50 μg/dose and 100 μg/dose of foralumab nasal compared to placebo
2. 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.

Conditions

Secondary Progressive Multiple Sclerosis

Keywords

Secondary Multiple Sclerosis; Progressive; Non-active; Double-blind; Nasal Foralumab; Placeb-controlled; Randomized; Phase 2a; Anti-CD3 monoclonal antibody

Outcome Measures

Primary Outcomes (3)

• The number of patients with adverse event (AE) reports.

  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).

  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.

  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).

Secondary Outcomes (3)

• Changes in the Expanded Disability Status Scale (EDSS).

  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).

  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).

  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).

Other Outcomes (3)

• Changes in the mean number of gadolinium-enhancing lesions per T1-weighted MRI scan, as measured by 3T MRI.

  Subjects will have a 3T T1-weighted MRI prior to Week 1 dosing (within 14 days before) and after Week 12 dosing (within 7 days).

• Changes in percent brain volume change by 3T MRI analysis pipeline between the Screening Visit (Baseline) and after 3 months of treatment, as measured by 3T MRI.

  Subjects will have a 3T T1-weighted MRI prior to Week 1 dosing (within 14 days before) and after Week 12 dosing (within 7 days).

• Paramagnetic rim lesions by quantitative susceptibility mapping sequences on MRI, as measured by 3T MRI (if center is able).

  Subjects will have a 3T T1-weighted MRI prior to Week 1 dosing (within 14 days before) and after Week 12 dosing (within 7 days).

Study Arms (3)

Nasal Foralumab 50 μg

EXPERIMENTAL

Each patient will receive nasal foralumab 50 μg per dosing day (25 μg per nostril).

Drug: Foralumab

Nasal Foralumab 100 μg

EXPERIMENTAL

Each patient will receive nasal foralumab 100 μg per dosing day (50 μg per nostril).

Drug: Foralumab

Nasal placebo (acetate buffer)

PLACEBO COMPARATOR

Each patient will receive placebo on each dosing day in divided doses, in each nostril.

Other: Placebo

Interventions

Foralumab DRUG

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.

Nasal Foralumab 100 μg; Nasal Foralumab 50 μg

Placebo OTHER

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).

Nasal placebo (acetate buffer)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Corticosteroid use (oral or intravenous) within the last 60 days or anticipated need for such treatment during the study period.
• Current use or use within 30 days prior to the screening visit of interferon, glatiramer acetate, fingolimod, siponimod, dimethyl fumarate, ponesimod, ozanimod, cyclosporin, methotrexate, azathioprine, mycophenolate mofetil, natalizumab or any other chronic immunosuppressive medication. Concomitant immunomodulatory or immunosuppressant treatments for MS are not permitted during study participation.
• Patient in whom the need to start or stop other pharmacologic treatment for MS is expected during the time of the study or the need for initiation of B cell depleting therapies (e.g. ocrelizumab, ofatumumab, rituximab) during the study.
• Use of B cell depleting therapies (e.g. ocrelizumab, ofatumumab, rituximab) within the prior 6 months. Or use of terifluonimide within the previous 6 months.
• Patients with any previous exposure to alemtuzumab, cyclophosphamide, cladribine, mitoxantrone, or daclizumab.
• Prior use of AHSCT or stem cell therapy.
• Inability to tolerate nasally administered medications.
• Nasal corticosteroids, nasal antihistamines, nasal flu dosing within the past 60 days.
• Active COVID-19 disease; according to FDA guidelines.
• Female patient who is pregnant, lactating, breastfeeding, or planning on becoming pregnant during the study. Female patients of childbearing age will undergo a serum pregnancy test at screening and be excluded from the study if positive. Urine pregnancy testing will be carried out prior to each dosing cycle, and the patient's study participation will be stopped if there is a positive result. Pregnancy testing will also be performed prior to each MRI or PET imaging session and participation in the imaging session and the study will be terminated if positive.
• Any history of malignancy or active malignancy.
• Inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus, asthma, or type 1 diabetes.
• Patients with a history of gadolinium allergy or any other contraindications to MRI, such as metal implants, chronic renal disease, and an eGRF of \<30 mL/minute or claustrophobia, or who are unable to lay flat in the PET or MRI scanner for the duration of the studies.
• A low affinity translocator protein (TSPO) binder (for PET ligand \[18F\]PBR06) determined by having a Thr/Thr polymorphism in the TSPO gene at screening.
• EBV IgM-positive patients, assessed at screening. Patients will also be excluded if they have a documented history of being EBV positive, even if the testing at screening is negative.

Sponsors & Collaborators

• Tiziana Life Sciences LTD: lead

Study Sites (7)

Yale

North Haven, Connecticut, 06473, United States

RECRUITING

Johns Hopkins

Baltimore, Maryland, 21287, United States

RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

University of Massachusetts

Worcester, Massachusetts, 01655, United States

RECRUITING

University of Buffalo

Buffalo, New York, 14202, United States

RECRUITING

Cornell Weill Medical Center

New York, New York, 10021, United States

RECRUITING

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

Related Publications (4)

• Nasal anti-CD3 monoclonal antibody (Foralumab) reduces PET microglial activation and blood inflammatory biomarkers in a patient with non-active secondary progressive MS. 2022, The Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, National Harbor, MD, US.

  BACKGROUND

• Nasal anti-CD3 monoclonal antibody (Foralumab) reduces PET microglial activation and blood inflammatory biomarkers in two patients with non-active secondary progressive multiple sclerosis. 2022, European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Annual Congress, Amsterdam, ND.

  BACKGROUND

• Treatment of six non-active secondary progressive MS patients with nasal anti-CD3 monoclonal antibody (Foralumab): safety, biomarker, and disability outcomes. 2023, European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Annual Congress, Milan, IT.

  BACKGROUND

• Treatment of PIRA with nasal foralumab dampens microglial activation and stabilizes clinical progression in non-active secondary progressive MS. 2024, American Academy of Neurology (AAN) Annual Meeting, Denver, CO, US.

  BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive

Interventions

foralumab

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Tiziana

CONTACT

1-833-849-4262; ms@tizianalifesciences.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The treating physician, study staff, and patients will be blinded to treatment. The research pharmacy at each site will have the treatment code assignments.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2024
• First Posted: March 5, 2024
• Study Start: November 15, 2023
• Primary Completion: November 1, 2025
• Study Completion: November 1, 2025
• Last Updated: October 15, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)