A Phase 2a Study of Foralumab Nasal in Patients With Multiple System Atrophy (MSA)

NCT06868628 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 2025P000259
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase 2a Study of Foralumab Nasal in Patients with Multiple System Atrophy (MSA)

Conditions

Multiple System Atrophy

Outcome Measures

Primary Outcomes (2)

• Change from Screening to Month 6 in the total MDS-UMSARS score

  From Screening to Month 6

• Change in TSPO activity as measured by [F-18]PBR06 retention calculated over whole brain and within key regions of interest (ROIs) at 6 months as compared to screening

  From Screening to Month 6

Secondary Outcomes (9)

• Change from Screening to Month 6 in MDS-UMSARS Part III (motor examination) score

  From Screening to Month 6

• Proportion of patients with ≥30% improvement in MDS-UMSARS total score at Month 6

  From Screening to Month 6

• Change from Screening to Month 6 in COMPASS-31 total score

  From Screening to Month 6

• Change from Screening to Month 6 in MSA-QoL summary index score

  From Screening to Month 6

• Percent whole brain volume change (PWBVC) between screening and 6 months

  From Screening to Month 6

Study Arms (1)

Foralumab Nasal

EXPERIMENTAL

This study includes a 6-month observational lead-in phase followed by a 6-month open-label treatment phase with Foralumab Nasal.

Drug: Foralumab Nasal

Interventions

Foralumab Nasal DRUG

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.

Foralumab Nasal

Eligibility Criteria

• Age: 30 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with a clinical diagnosis of Clinically Established or Clinically Probable Multiple System Atrophy in accordance with 2022 MDS diagnostic criteria.
• Age 30 to 85 years, at the time of signing the informed consent.
• Stable dopaminergic treatment for at least 4 weeks before enrollment.
• Adequate hematologic parameters without ongoing transfusion support: Hemoglobin (Hb) ≥ 9 g/dL; Platelets ≥ 100 x 109 cells/L.
• Creatinine ≤ 1.5 x the upper limit of normal (ULN), or calculated creatinine clearance ≥ 60 mL/minute x 1.73 m2 per the Cockcroft-Gault formula.
• Total bilirubin ≤ 2 times the upper limit of normal (ULN) unless due to Gilbert's disease.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times ULN.
• QT interval corrected for rate (QTcF) ≤ 470 msec for women and ≤ 450 msec for men on the ECG obtained at Screening.
• Negative urine pregnancy test within 7 days prior to the first dose of study therapy for women of child-bearing potential (WCBP), 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 WCBP and male patients 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.
• Patients whose immunizations are fully up to date at the Screening, according to the assessment of their primary care physician and neurologist.
• Ability to provide written informed consent.

You may not qualify if:

• Diagnosis or suspicion of other cause for Parkinsonism or a known alternate neurologic diagnosis.
• Female patient who is pregnant, lactating, breastfeeding, or planning to become pregnant during study.
• Individuals with claustrophobia who cannot tolerate the study procedures
• Non-MRI-compatible implanted devices.
• Low-affinity binders for translocator protein (TSPO) PET ligands.
• Systemic corticosteroid treatment in the past four weeks (excluding nasal or local treatment).
• Individuals with significant cognitive impairment (i.e., MoCA score less than or equal to 20).
• Brain MRI indicative of significant abnormalities that interfere with PET-MRI co-registration (i.e., large prior hemorrhage or multiple infarcts).
• Serious cardiac condition within the last 6 months, such as uncontrolled arrhythmia, myocardial infarction, unstable angina, or heart disease defined by the New York Heart Association (NYHA) Class III or Class IV or hereditary long QT syndrome.
• Concomitant medication(s) that may cause QTc prolongation or induce Torsades de Pointes, except for antimicrobials that are used as standard of care to prevent or treat infections and other such drugs that are considered by the Investigator to be essential for patient care.
• Patients who test positive for human immunodeficiency virus (HIV), hepatitis B virus surface antigen (HBsAg), hepatitis C virus (HCV) or positive Epstein-Barr virus (EBV) IgM at the Screening Visit.
• Past medical history of a hematologic or solid malignancy.
• Treatment with chronic immunosuppressives such as interferon, glatiramer acetate, fingolimod, Siponimod, dimethyl fumarate, or natalizumab within the past 90 days.
• Inability to tolerate nasally administered medications.
• Nasal corticosteroids, nasal antihistamines, nasal flu dosing within the past 30 days, or anticipated need during the study.

Sponsors & Collaborators

• Tiziana Life Sciences LTD: lead

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Related Publications (18)

• Wenning GK, Stankovic I, Vignatelli L, Fanciulli A, Calandra-Buonaura G, Seppi K, Palma JA, Meissner WG, Krismer F, Berg D, Cortelli P, Freeman R, Halliday G, Hoglinger G, Lang A, Ling H, Litvan I, Low P, Miki Y, Panicker J, Pellecchia MT, Quinn N, Sakakibara R, Stamelou M, Tolosa E, Tsuji S, Warner T, Poewe W, Kaufmann H. The Movement Disorder Society Criteria for the Diagnosis of Multiple System Atrophy. Mov Disord. 2022 Jun;37(6):1131-1148. doi: 10.1002/mds.29005. Epub 2022 Apr 21.

  PMID: 35445419 BACKGROUND

• Singhal T, Cicero S, Rissanen E, Ficke J, Kukreja P, Vaquerano S, Glanz B, Dubey S, Sticka W, Seaver K, Kijewski M, Callen AM, Chu R, Carter K, Silbersweig D, Chitnis T, Bakshi R, Weiner HL. Glial Activity Load on PET Reveals Persistent "Smoldering" Inflammation in MS Despite Disease-Modifying Treatment: 18 F-PBR06 Study. Clin Nucl Med. 2024 Jun 1;49(6):491-499. doi: 10.1097/RLU.0000000000005201. Epub 2024 Apr 17.

  PMID: 38630948 BACKGROUND

• Singhal T, O'Connor K, Dubey S, Pan H, Chu R, Hurwitz S, Cicero S, Tauhid S, Silbersweig D, Stern E, Kijewski M, DiCarli M, Weiner HL, Bakshi R. Gray matter microglial activation in relapsing vs progressive MS: A [F-18]PBR06-PET study. Neurol Neuroimmunol Neuroinflamm. 2019 Jul 1;6(5):e587. doi: 10.1212/NXI.0000000000000587. eCollection 2019 Sep.

  PMID: 31355321 BACKGROUND

• Shahnawaz M, Mukherjee A, Pritzkow S, Mendez N, Rabadia P, Liu X, Hu B, Schmeichel A, Singer W, Wu G, Tsai AL, Shirani H, Nilsson KPR, Low PA, Soto C. Discriminating alpha-synuclein strains in Parkinson's disease and multiple system atrophy. Nature. 2020 Feb;578(7794):273-277. doi: 10.1038/s41586-020-1984-7. Epub 2020 Feb 5.

  PMID: 32025029 BACKGROUND

• Owen DR, Yeo AJ, Gunn RN, Song K, Wadsworth G, Lewis A, Rhodes C, Pulford DJ, Bennacef I, Parker CA, StJean PL, Cardon LR, Mooser VE, Matthews PM, Rabiner EA, Rubio JP. An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28. J Cereb Blood Flow Metab. 2012 Jan;32(1):1-5. doi: 10.1038/jcbfm.2011.147. Epub 2011 Oct 19.

  PMID: 22008728 BACKGROUND

• Ndayisaba A, Pitaro AT, Willett AS, Jones KA, de Gusmao CM, Olsen AL, Kim J, Rissanen E, Woods JK, Srinivasan SR, Nagy A, Nagy A, Mesidor M, Cicero S, Patel V, Oakley DH, Tuncali I, Taglieri-Noble K, Clark EC, Paulson J, Krolewski RC, Ho GP, Hung AY, Wills AM, Hayes MT, Macmore JP, Warren L, Bower PG, Langer CB, Kellerman LR, Humphreys CW, Glanz BI, Dielubanza EJ, Frosch MP, Freeman RL, Gibbons CH, Stefanova N, Chitnis T, Weiner HL, Scherzer CR, Scholz SW, Vuzman D, Cox LM, Wenning G, Schmahmann JD, Gupta AS, Novak P, Young GS, Feany MB, Singhal T, Khurana V. Clinical Trial-Ready Patient Cohorts for Multiple System Atrophy: Coupling Biospecimen and iPSC Banking to Longitudinal Deep-Phenotyping. Cerebellum. 2024 Feb;23(1):31-51. doi: 10.1007/s12311-022-01471-8. Epub 2022 Oct 3.

  PMID: 36190676 BACKGROUND

• Moreira TG, Matos KTF, De Paula GS, Santana TMM, Da Mata RG, Pansera FC, Cortina AS, Spinola MG, Baecher-Allan CM, Keppeke GD, Jacob J, Palejwala V, Chen K, Izzy S, Healey BC, Rezende RM, Dedivitis RA, Shailubhai K, Weiner HL. Nasal Administration of Anti-CD3 Monoclonal Antibody (Foralumab) Reduces Lung Inflammation and Blood Inflammatory Biomarkers in Mild to Moderate COVID-19 Patients: A Pilot Study. Front Immunol. 2021 Aug 12;12:709861. doi: 10.3389/fimmu.2021.709861. eCollection 2021.

  PMID: 34475873 BACKGROUND

• Meissner WG, Remy P, Giordana C, Maltete D, Derkinderen P, Houeto JL, Anheim M, Benatru I, Boraud T, Brefel-Courbon C, Carriere N, Catala H, Colin O, Corvol JC, Damier P, Dellapina E, Devos D, Drapier S, Fabbri M, Ferrier V, Foubert-Samier A, Frismand-Kryloff S, Georget A, Germain C, Grimaldi S, Hardy C, Hopes L, Krystkowiak P, Laurens B, Lefaucheur R, Mariani LL, Marques A, Marse C, Ory-Magne F, Rigalleau V, Salhi H, Saubion A, Stott SRW, Thalamas C, Thiriez C, Tir M, Wyse RK, Benard A, Rascol O; LIXIPARK Study Group. Trial of Lixisenatide in Early Parkinson's Disease. N Engl J Med. 2024 Apr 4;390(13):1176-1185. doi: 10.1056/NEJMoa2312323.

  PMID: 38598572 BACKGROUND

• Lopes JR, Zhang X, Mayrink J, Tatematsu BK, Guo L, LeServe DS, Abou-El-Hassan H, Rong F, Dalton MJ, Oliveira MG, Lanser TB, Liu L, Butovsky O, Rezende RM, Weiner HL. Nasal administration of anti-CD3 monoclonal antibody ameliorates disease in a mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A. 2023 Sep 12;120(37):e2309221120. doi: 10.1073/pnas.2309221120. Epub 2023 Sep 5.

  PMID: 37669383 BACKGROUND

• Lavisse S, Goutal S, Wimberley C, Tonietto M, Bottlaender M, Gervais P, Kuhnast B, Peyronneau MA, Barret O, Lagarde J, Sarazin M, Hantraye P, Thiriez C, Remy P. Increased microglial activation in patients with Parkinson disease using [18F]-DPA714 TSPO PET imaging. Parkinsonism Relat Disord. 2021 Jan;82:29-36. doi: 10.1016/j.parkreldis.2020.11.011. Epub 2020 Nov 17.

  PMID: 33242662 BACKGROUND

• Kuzkina A, Bargar C, Schmitt D, Rossle J, Wang W, Schubert AL, Tatsuoka C, Gunzler SA, Zou WQ, Volkmann J, Sommer C, Doppler K, Chen SG. Diagnostic value of skin RT-QuIC in Parkinson's disease: a two-laboratory study. NPJ Parkinsons Dis. 2021 Nov 15;7(1):99. doi: 10.1038/s41531-021-00242-2.

  PMID: 34782640 BACKGROUND

• Jucaite A, Cselenyi Z, Kreisl WC, Rabiner EA, Varrone A, Carson RE, Rinne JO, Savage A, Schou M, Johnstrom P, Svenningsson P, Rascol O, Meissner WG, Barone P, Seppi K, Kaufmann H, Wenning GK, Poewe W, Farde L. Glia Imaging Differentiates Multiple System Atrophy from Parkinson's Disease: A Positron Emission Tomography Study with [11 C]PBR28 and Machine Learning Analysis. Mov Disord. 2022 Jan;37(1):119-129. doi: 10.1002/mds.28814. Epub 2021 Oct 5.

  PMID: 34609758 BACKGROUND

• Ishizawa K, Komori T, Sasaki S, Arai N, Mizutani T, Hirose T. Microglial activation parallels system degeneration in multiple system atrophy. J Neuropathol Exp Neurol. 2004 Jan;63(1):43-52. doi: 10.1093/jnen/63.1.43.

  PMID: 14748560 BACKGROUND

• Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ, Wood NW, Colosimo C, Durr A, Fowler CJ, Kaufmann H, Klockgether T, Lees A, Poewe W, Quinn N, Revesz T, Robertson D, Sandroni P, Seppi K, Vidailhet M. Second consensus statement on the diagnosis of multiple system atrophy. Neurology. 2008 Aug 26;71(9):670-6. doi: 10.1212/01.wnl.0000324625.00404.15.

  PMID: 18725592 BACKGROUND

• Fujimura Y, Zoghbi SS, Simeon FG, Taku A, Pike VW, Innis RB, Fujita M. Quantification of translocator protein (18 kDa) in the human brain with PET and a novel radioligand, (18)F-PBR06. J Nucl Med. 2009 Jul;50(7):1047-53. doi: 10.2967/jnumed.108.060186. Epub 2009 Jun 12.

  PMID: 19525468 BACKGROUND

• Chitnis T, Kaskow BJ, Case J, Hanus K, Li Z, Varghese JF, Healy BC, Gauthier C, Saraceno TJ, Saxena S, Lokhande H, Moreira TG, Zurawski J, Roditi RE, Bergmark RW, Giovannoni F, Torti MF, Li Z, Quintana F, Clementi WA, Shailubhai K, Weiner HL, Baecher-Allan CM. Nasal administration of anti-CD3 monoclonal antibody modulates effector CD8+ T cell function and induces a regulatory response in T cells in human subjects. Front Immunol. 2022 Nov 23;13:956907. doi: 10.3389/fimmu.2022.956907. eCollection 2022.

  PMID: 36505477 BACKGROUND

• Chatenoud L, Bluestone JA. CD3-specific antibodies: a portal to the treatment of autoimmunity. Nat Rev Immunol. 2007 Aug;7(8):622-32. doi: 10.1038/nri2134. Epub 2007 Jul 20.

  PMID: 17641665 BACKGROUND

• Brochard V, Combadiere B, Prigent A, Laouar Y, Perrin A, Beray-Berthat V, Bonduelle O, Alvarez-Fischer D, Callebert J, Launay JM, Duyckaerts C, Flavell RA, Hirsch EC, Hunot S. Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease. J Clin Invest. 2009 Jan;119(1):182-92. doi: 10.1172/JCI36470. Epub 2008 Dec 22.

  PMID: 19104149 BACKGROUND

MeSH Terms

Conditions

Multiple System Atrophy

Condition Hierarchy (Ancestors)

Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Central Study Contacts

Brigham and Women's Hospital Movement Research Team

CONTACT

507-491-0272; BWHMovementResearch@bwh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2025
• First Posted: March 11, 2025
• Study Start: May 19, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: September 23, 2025

Record last verified: 2025-09

Locations

US (1)