The BANYAN Trial, an ALS MyMatch Trial Evaluating Safety, Biomarker Activity, and Microglial Activation of Nasal Foralumab (BANYAN)

A Phase 2a Randomized, Double-Blind Study to Evaluate the Safety, Biomarker Activity, and Microglial Activation of Nasal Foralumab in Patients With Amyotrophic Lateral Sclerosis (ALS)

The goal of this clinical trial is to learn whether a nasal spray medicine called foralumab is safe and easy to tolerate in adults with amyotrophic lateral sclerosis (ALS). ALS is a disease that slowly damages the nerve cells that control movement, causing muscles to grow weaker over time. Foralumab is being studied as a possible way to calm the inflammation and immune system activity that are thought to play a role in ALS.

The main questions it aims to answer are:

1. Is nasal foralumab safe for people with ALS, and how well do they tolerate it over 12 and 24 weeks of treatment?
2. Does foralumab change certain markers in the blood and spinal fluid, and lower inflammation in the brain, compared with a placebo?

Researchers will compare people who take foralumab to people who take a placebo (a matching nasal spray with no medicine in it) to see how the two groups differ in safety and in these markers.

About 44 adults aged 18 to 75 with ALS will take part. For the first 12 weeks, participants will be randomly assigned so that about 3 in 4 use foralumab and about 1 in 4 use the placebo. Neither the participants nor the study staff will know who is using which during this time (this is called "double-blind"). After the first 12 weeks, everyone who continues will use foralumab for the next 12 weeks.

Participants will:

• Spray the study treatment into both nostrils 3 times a week, on alternate days, in cycles of 2 weeks on treatment followed by 1 week off
• Learn to use the nasal spray device so they or a caregiver can give most doses at home
• Take part for about 8.5 months in total, which includes screening, 24 weeks of treatment, and a safety check-in about 4 weeks after the last dose
• Attend some visits at the study clinic and complete others remotely by phone or video
• Have study tests that may include blood samples, breathing and muscle-strength checks, and - for those who agree and at certain study centers - spinal fluid samples and brain scans to measure inflammation

Study Overview

• Status: Not yet recruiting
• Conditions: ALS (Amyotrophic Lateral Sclerosis); ALS; ALS - Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: Foralumab Nasal; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 44
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults ≥18 years of age and ≤75 years of age with a diagnosis of symptomatic ALS by revised El Escorial Criteria (clinically possible, probable, probable lab-supported, or definite).
• Participant must be actively enrolled and must have met eligibility criteria for the Healey ALS MyMatch Common Screening Protocol (MCSP) AND determined to have met preliminary eligibility on targeted medical history and review of systems and safety laboratory results required for this trial.
• Blood neurofilament (NfL) level of greater than 40 pg/mL as measured by the MyMatch Common Screening Protocol specific NfL assay.
• Ability to provide written informed consent.
• Less than or equal to 24-months since onset of weakness or spasticity attributed to ALS.
• Slow vital capacity (SVC) of at least 65% predicted value for gender, height and age at trial screening visit.
• Participant must not have taken riluzole and/or edaravone for at least 30 days, or be on a stable dose of riluzole and/or edaravone for at least 30 days prior to baseline (riluzole-naïve or edaravone-naïve participants are permitted in the study).
• Negative urine pregnancy test within 7 days prior to the first dose of study therapy for women of child-bearing potential, defined as a sexually mature woman who has not undergone a hysterectomy or who has not been naturally postmenopausal for at least 24 consecutive months (i.e., who has had menses any time in the preceding 24 consecutive months). Sexually active women of child-bearing potential and male participants must agree to use highly effective methods to avoid pregnancy (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) throughout the study and for 90 days after the completion of study treatment.
• Participants must be able to travel to the study site for study visits and complete required study procedures.
• Participants who are participating in the PET or Lumbar Puncture (LP) outcomes, must be determined to be able to safely tolerate these study procedure(s) in the opinion of the study investigator AND as determined by the targeted medical history and review of systems in the MCSP. Both procedures are highly encouraged.
• Participants whose immunizations are fully up to date at Screening, according to the assessment of their primary care physician and neurologist.

Exclusion Criteria:

• Clinically significant medical condition that would pose a risk to the participant, according to the PI's judgment and examination prior to baseline.
• Active ENT disease (such as allergic rhinitis, chronic rhinitis, active sinusitis treated within the past 30 days or deemed as clinically relevant, clinically significant deviated nasal septum, nasal polyps) that might interfere with safely administering the drug nasally.
• Active clinically significant infection or immunocompromised condition.
• Treatment with chronic immunosuppressants or other immunosuppressants within the past 90 days.
• Concomitant use of investigational treatments for ALS within 5 half-lives or 30 days prior to the Baseline visit, whichever is longest (high dosage methylcobalamin permitted).
• Exposure to any gene or cell therapies under investigation for treatment of ALS.
• Inability to tolerate nasally administered medications.
• Participant reported history of any vaccines within past 14 days (prior to first dose of foralumab).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Foralumab placebo nasal solution is a preservative-free, sterile, clear, colorless-to-slightly-yellow solution filled in an Aptar Unidose nasal atomizer device. Participants will complete eight 3-week dosing cycles over the study. During each cycle, Foralumab placebo nasal solution will be administered intranasally three times per week for the first two weeks, with no administration in the third week.
Experimental: Foralumab	Drug: Foralumab Nasal; Foralumab is an anti-CD3 monoclonal antibody administered as a nasal spray. Participants will complete eight 3-week dosing cycles over the study. During each cycle, Foralumab will be administered intranasally three times per week for the first two weeks, with no administration in the third week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety - Occurrence of serious and non-serious treatment emergent adverse events and clinically significant treatment emergent abnormalities.	The occurrence of serious (inclusive of SUSARs) and non-serious treatment emergent adverse events (TEAEs) and clinically significant treatment-emergent abnormalities in clinical, including vital signs (heart rate, blood pressure, weight) and laboratory values (reported as AEs) over both 12 (4 cycles) and 24 (8 cycles) week treatment periods in the Safety population.	12 weeks and 24 weeks
Tolerability - Percentage of participant that complete 12 or 24 weeks of study treatment.	the percentage of nasal foralumab treated participants in the Safety population who complete four (12-weeks) or eight (24-weeks) cycles of study treatment without study drug attributed intolerable AEs or SAEs or AESIs that lead to early permanent drug discontinuation.	12 and 24 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune Reconstitution Changes: change in blood Tregs and functional T cell markers on flow cytometry	Evaluate immune reconstitution changes from baseline following 4 cycles of foralumab 50 μg dosage treatment compared to placebo, as measured by blood Treg number and functional T cell markers including CD4+ T cell subset profiles on flow cytometry	12 weeks
Immunological gene expression changes: single cell RNA sequencing	Evaluate immune reconstitution changes from baseline following 4 cycles of foralumab 50 μg dosage treatment compared to placebo, as measured by blood Treg number and functional T cell markers including CD4+ T cell subset profiles on flow cytometry	12 weeks
Neurofilament light changes	evaluate plasma and CSF neurofilament light (pNfL) changes from baseline following 4 cycles of foralumab 50 μg dosage treatment compared to placebo.	12 weeks

Collaborators and Investigators

• Sponsor: Tiziana Life Sciences LTD

Study record dates

Study Major Dates

• Study Start (Estimated): July 25, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: June 30, 2026
• First Submitted That Met QC Criteria: June 30, 2026
• First Posted (Actual): July 7, 2026

Study Record Updates

• Last Update Posted (Actual): July 7, 2026
• Last Update Submitted That Met QC Criteria: June 30, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Neuroinflammation; Lou Gehrig's Disease; Anti-CD3; Anti-CD3 monoclonal antibody; Foralumab; Nasal foralumab
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Neuromuscular Diseases; Metabolic Diseases; Inflammation; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Neuroinflammatory Diseases; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: TILS-ALS-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No