Nasal Foralumab for Multiple Sclerosis

(TILS-022 Trial)

Overseen By William Clementi, PharmD FCP

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Tiziana Life Sciences LTD

Must not be taking: Corticosteroids, Immunosuppressants, B cell depleters

Disqualifiers: Pregnancy, Malignancy, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

55 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, especially those that affect the immune system, like corticosteroids and other immunosuppressive drugs, at least 30 to 60 days before starting the study. If you're on any of these medications, you'll need to stop them before participating.

How is nasal Foralumab different from other multiple sclerosis drugs?

Nasal Foralumab is unique because it is administered through the nose, which is different from most multiple sclerosis treatments that are given by injection or infusion. This nasal route may offer a more convenient and potentially less invasive option for patients. ^{1 2 3 4 5}

What is the purpose of this trial?

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.

Eligibility Criteria

This trial is for patients who have completed the TILS-021 study for non-active secondary progressive multiple sclerosis. Participants will receive nasal Foralumab, initially at a lower dose which may be increased based on their clinical status.

Inclusion Criteria

My vaccinations are current, considering my health and treatments.

Adequate hematologic parameters without ongoing transfusion support: Hemoglobin (Hb) ≥ 9 g/dL, Platelets ≥ 100 x 10^9 cells/L

Subjects must have enrolled in and successfully completed TILS-021 within the preceding 90 days, including End of Treatment and End of Study assessments

Exclusion Criteria

Subjects that terminated TILS-021 early as defined by not undergoing End of Study visit

I have had a stem cell transplant using my own cells.

I have not taken certain medications in the last 30 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nasal foralumab 50 µg three days a week for two weeks, followed by a one-week rest, in 3-week cycles. Dose may be escalated to 100 µg at week 12.

24 weeks

Weekly visits (in-person or virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term, pending FDA approval

Long-term

Treatment Details

Interventions

• Foralumab

Trial Overview The trial tests nasal Foralumab in a 6-month open-label extension where all participants start with a low dose that can be escalated. It's designed to give those from a previous placebo-controlled study access to the drug and assess longer-term effects.

Participant Groups

Group I: Nasal foralumab 50 μg per dosing day (25 μg per nostril) Experimental Treatment 1 Intervention

All patients will initially receive nasal foralumab 50 µg three (3) days a week (Monday-Wednesday-Friday) for two weeks, followed by a one-week rest, comprising 3-week cycles.

Who Is Running the Clinical Trial?

Tiziana Life Sciences LTD

Lead Sponsor

Trials

13

Recruited

310+

Findings from Research

In a retrospective study of 50 patients treated with intravenous ofatumumab for multiple sclerosis and related disorders over a median duration of 2.2 years, the annualized relapse rate significantly decreased from 1.03 to 0.38, indicating effective disease control.

While ofatumumab treatment showed a stabilization of disability worsening (7% at 24 months), there was a high incidence of infusion-related reactions (86% during the first infusion), suggesting a need for careful monitoring during administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous ofatumumab treatment of multiple sclerosis and related disorders: An observational study. El Mahdaoui, S., Romme Christensen, J., Magyari, M., et al.[2022]

In phase 3 trials, patients with relapsing-remitting multiple sclerosis treated with alemtuzumab showed significant improvements in quality of life (QoL) across multiple measures, including physical, mental, and emotional aspects, sustained through Year 2.

Alemtuzumab demonstrated greater QoL improvements compared to subcutaneous interferon beta-1a at all time points, indicating its superior efficacy in enhancing the overall well-being of patients, regardless of their treatment history.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alemtuzumab improves quality-of-life outcomes compared with subcutaneous interferon beta-1a in patients with active relapsing-remitting multiple sclerosis. Arroyo González, R., Kita, M., Crayton, H., et al.[2018]

Ofatumumab is an all-human monoclonal antibody that effectively reduces the frequency of exacerbations and the risk of disability progression in patients with multiple sclerosis, showing better results compared to teriflunomide.

This drug can be used as a second-line therapy for patients with active relapsing MS or secondary progressive MS, especially for those who have not responded to first-line treatments or have a high risk of progressive multifocal leukoencephalopathy (PML).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ofatumumab - a new drug for the treatment of multiple sclerosis]. Boyko, AN., Smirnova, NF., Shchukin, IA., et al.[2021]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Intravenous ofatumumab treatment of multiple sclerosis and related disorders: An observational study. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Alemtuzumab improves quality-of-life outcomes compared with subcutaneous interferon beta-1a in patients with active relapsing-remitting multiple sclerosis. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Alemtuzumab treatment in Denmark: A national study based on the Danish Multiple Sclerosis Registry. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Alemtuzumab outcomes by age: Post hoc analysis from the randomized CARE-MS studies over 8 years. [2021]

5. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Ofatumumab - a new drug for the treatment of multiple sclerosis]. [2021]