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

Phase 2

Recruiting

• Conditions: Secondary Progressive Multiple Sclerosis
• Interventions: Drug: Foralumab; Other: Placebo

• Registration Number: NCT06292923
• Lead Sponsor: Tiziana Life Sciences LTD

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. 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.

Detailed Description

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 Timeline

• Study Start: 2023-11-15
• Study First Submitted: 2024-02-02
• Study First Submitted QC: 2024-02-27
• Status Verified: 2024-03
• Study First Posted: 2024-03-05
• Last Update Submitted: 2024-03-15
• Last Update Posted: 2024-03-19
• Primary Completion: 2024-11
• Study Completion: 2024-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 54

Inclusion Criteria

Not provided

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Exclusion Criteria

1. Corticosteroid use (oral or intravenous) within the last 60 days or anticipated need for such treatment during the study period.
2. 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.
3. 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.
4. 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.
5. Patients with any previous exposure to alemtuzumab, cyclophosphamide, cladribine, mitoxantrone, or daclizumab.
6. Prior use of AHSCT or stem cell therapy.
7. Inability to tolerate nasally administered medications.
8. Nasal corticosteroids, nasal antihistamines, nasal flu dosing within the past 60 days.
9. Active COVID-19 disease; according to FDA guidelines.
10. 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.
11. Any history of malignancy or active malignancy.
12. Inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus, asthma, or type 1 diabetes.
13. 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.
14. 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.
15. 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.
16. Known positivity for human immunodeficiency virus (HIV), hepatitis B virus surface antigen (HBsAg), or hepatitis C virus (HCV) or tuberculosis at screening. If the patient has a history of positivity for any of these diseases, they are excluded even if current screening is negative.
17. Patients with a neutrophil count at baseline of <1000 cells/mL or lymphocytes <500 cells/mL.
18. Any nasal pathology such as clinically significant deviated septum, nasal polyps, chronic rhinitis, or a history of sinusitis diagnosed or treated in the past 12 months.
19. Clinically significant cardiac condition or ECG abnormality at screening or by history. An ECG will be done prior to each dosing cycle and patients will be excluded or treatment discontinued for any significant ECG abnormality.
20. Any other medical intervention or other condition which, in the opinion of the Principal Investigator, could compromise adherence to study requirements or confound the interpretation of study results.
21. A history of recent infections or treatment for infections.
22. Receipt of an investigational drug/biological product in the past 30 days of screening, or concurrent receipt of an investigational during this study, other than the product under study. Patients may not have previously received treatment with foralumab nasal.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Nasal Foralumab 100 μg	Foralumab	Each patient will receive nasal foralumab 100 μg per dosing day (50 μg per nostril).
Nasal placebo (acetate buffer)	Placebo	Each patient will receive placebo on each dosing day in divided doses, in each nostril.
Nasal Foralumab 50 μg	Foralumab	Each patient will receive nasal foralumab 50 μg per dosing day (25 μg per nostril).

Primary Outcome Measures

Name	Time	Method
Change from baseline for [18F]PBR06-positron emission tomography (PET) scans for microglial activation after 12 weeks (3 months) of study treatment.	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).	Subjects at all sites will undergo PET imaging with the radiotracer \[18F\]PBR06.
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).	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).	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).

Secondary Outcome Measures

Name	Time	Method
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).	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.
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).	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.
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).	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.

Trial Locations

Locations (1)

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States