Phase 2a INFORM-MS Trial to Study Anti-CD3 Agent Foralumab in Nonactive Secondary Progressive MS

At the 2025 European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress, held September 24-26, in Barcelona, Spain, researchers shared the design of a placebo-controlled, phase 2a trial, dubbed INFORM-MS (NCT06292923), that tests the efficacy and safety of nasal foralumab (Tiziana Life Sciences) in patients with nonactive secondary progressive multiple sclerosis (naSPMS).^1,2

This multicenter, parallel-group study includes 54 patients with na-SPMS who are randomly assigned to either 2 doses of foralumab (50 μg or 100 μg), an anti-CD3 antibody, or placebo, for a 12-week treatment period. In addition to safety and tolerability, the study employs a unique primary outcome of change in microglial activation as measured by [¹⁸F]PBR06 TSPO PET.

"We are pleased to share the design of our Phase 2a trial of nasal foralumab with the MS research community at ECTRIMS," Ivor Elrifi, chief executive officer at Tiziana, said in a statement.² "This clinical trial represents an important step forward in our mission to develop innovative therapies for patients living with non-active secondary progressive multiple sclerosis, a population with limited treatment options."

As of March 31, 2025, 17 of the expected 54 patients had been enrolled, with 9 randomized to treatment, and 7 who completed the core phase of the study. In May, preliminary data from 10 patients in the trial showed that all treated participants had stabilization of their Expanded Disability Status Scale scores, with 3 of 4 patients that were treated continuously for 12 months who showed improvement. Fatigue, a major symptom burden in MS, improved in 6 of the 10 patients, as measured by the Modified Fatigue Impact Scale.

READ MORE: Tolebrutinib Preserves Notable MS Quality of Life Features in Non-Relapsing Secondary Progressive Multiple Sclerosis

For INFORM-MS, changes from baseline are assessed using a T-distribution, while response rates will be reported with exact Clopper-Pearson confidence intervals. Between-group differences in response will be evaluated using 90% confidence intervals calculated by the Newcombe-Wilson method.

The trial includes patients with a confirmed diagnosis of na-SPMS per the 2017 McDonald criteria, as well as documented disability progression despite at least 2 years of prior disease-modifying therapy. Patients are excluded if they recently received corticosteroids, immunosuppressants, or B-cell–depleting therapies, or if they have prior exposure to high-risk agents like alemtuzumab or mitoxantrone. Other key exclusions include pregnancy, active infection (e.g., HIV, hepatitis, TB), significant nasal disease preventing study drug delivery, MRI contraindications, or serious comorbidities that could interfere with study participation.³

Additional highlights from the study shared in May showed that total MFIS scores correlated with mGALP scores in the hippocampus (r = 0.89; P = .007) at baseline. At the 6-month mark, no new T2 lesions were observed on MRI, and TSPO-PET imaging demonstrated significant reductions in microglial activation (P <.05). Notably, single-cell RNA sequencing revealed early and sustained changes in peripheral immune cells, including increased regulatory T cells and expression of TGFß across multiple cell types.

At the time, principal investigator Tanuja Chitnis, MD, said in a statement that the findings, "mark a significant advancement for patients living with non-active Secondary Progressive MS, who currently have very limited treatment options.” Chitnis, who serves as a professor of neurology at Harvard Medical School, added, “Nasal administration of foralumab represents a novel, non-invasive approach that not only induces regulatory immunity but also reduces harmful CNS inflammation."

Intranasal foralumab remains in development as a treatment for multiple system atrophy (MSA), with an ongoing phase 2a trial (NCT06868628) that recently kicked off last month. The small-scale study, which remains currently enrolling, includes a 6-month observational lead-in phase followed by a 6-month open-label treatment phase with foralumab. The primary outcome is change in MDS-Unified Multiple System Atrophy Rating Scale score over a 6-month period, as well as change in TSPO activity as measured by [¹⁸F]PBR06 TSPO PET.⁵

Click here for more ECTRIMS 2025 coverage.

REFERENCES
1. INFORM-MS: Study design of a Phase 2a double blind placebo-controlled trial of nasal foralumab in non-active secondary progressive multiple sclerosis. Presented at: 2025 ECTRIMS Congress; September 24-26; Barcelona, Spain. Abstract P338.
2. Tiziana Life Sciences Announces Poster Presentation on Intranasal Foralumab Clinical Trial at the 41st ECTRIMS Congress. News release. Tiziana Life Sciences. September 24, 2025. Accessed September 24, 2025. https://www.tizianalifesciences.com/tiziana-life-sciences-announces-poster-presentation-on-intranasal-foralumab-clinical-trial-at-the-41st-ectrims-congress/
3. A Study of Nasal Foralumab in Non-Active Secondary Progressive Multiple Sclerosis Patients. Clinicaltrials.gov. Updated August 28, 2025. Accessed September 24, 2025. https://www.clinicaltrials.gov/study/NCT06292923
4. Tiziana Life Sciences Announces Comprehensive Positive Results from Study of Nasal Foralumab in Patients with Multiple Sclerosis. News release. Tiziana Life Sciences. May 6^th, 2025. Accessed September 24, 2025. https://www.tizianalifesciences.com/tiziana-life-sciences-announces-comprehensive-positive-results-from-study-of-nasal-foralumab-in-patients-with-multiple-sclerosis
5. Tiziana Life Sciences Doses First Patient in Phase 2a Trial of Intranasal Foralumab for Multiple System Atrophy. News release. Tiziana Life Sciences. August 14, 2025. Accessed September 24, 2025. https://www.tizianalifesciences.com/tiziana-life-sciences-doses-first-patient-in-phase-2a-trial-of-intranasal-foralumab-for-multiple-system-atrophy/