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

Summary

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

Timeline

Start

2025-05-19

Primary completion

2027-04-01

Completion

2027-04-01

Publications

• Background 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Drugs

Indications