A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability and Activity of Ibudilast (MN-166) in Subjects with Progressive Multiple Sclerosis

Multiple Sclerosis (MS) is a chronic, inflammatory demyelinating disease of the central nervous system that affects 400,000 people in the US and 2 million people worldwide. Those affected with the disease are characterized by their progression into one of three variants: relapsing-remitting, secondary-progressive and primary-progressive. Despite recent improvements in pharmacotherapy for relapsing-remitting Multiple Sclerosis (RRMS), there are no therapies with demonstrated efficacy in progressive Multiple Sclerosis in the absence of relapses.

NN102 is a study to determine the safety, tolerability and activity of ibudilast (MN-166) administered twice daily over a 96 week period in subjects with primary and secondary-progressive multiple sclerosis. A total of 255 subjects were randomly assigned to two treatment arms (ibudilast or matching-placebo), and the study utilized advanced brain imaging to assess activity and correlate clinical activity with these imaging measures.

Ibudilast demonstrated a statistically significant reduction in the rate of progression of whole brain atrophy compared to placebo, as measured by MRI analysis using brain parenchymal fraction. Additionally, ibudilast was found to be safe and well-tolerated. These results represent “an encouraging step forward in the development of treatments for progressive MS, which has historically been very difficult to treat,” according to Robert Fox, MD, NN102 SPRINT-MS PI.

NN102 was supported by NINDS (U01 NS082329) in partnership with Medicinova and the National Multiple Sclerosis Society.

Protocol Principal Investigator: 
Contact Information: 

CCC Project Managers: Akshata Ashokkumar, Andrea Ariza, Daniela Grasso

DCC Project Coordinator: Maxine Koepp

  • Ken Sakaie, Janel K Fedler, Jon W Yankey, Kunio Nakamura, Josef Debbins, Mark J Lowe, Paolo Raska, Robert J Fox Influence of equipment changes on MRI measures of brain atrophy and brain microstructure in a placebo-controlled trial of ibudilast in progressive multiple sclerosis. Multiple Sclerosis Journal - Experimental, Translational and Clinical2021 May 187(2)1-10.
    PubMed: PMC8138298

  • Naismith RT, Bernel RA, Coffey CS, Goodman AD, Fedler JK, Chase M, Klawiter EC, Nakamura K, Narayanan S, Goebel C, Yankey JW, Klingner EA, Fox RJ. Effects of Ibudilast on MRI measures in the Phase 2 SPRINT-MS Study. Neurology2021 January 96(4)e491-e500.
    PubMed: PMC7905793

  • Goodman AD, Fedler JK, Yankey J, Klingner EA, Ecklund DJ, Goebel CV, Bernel RA, Chase M, Coffey CS, Klawiter EC, Naismith RT, Fox RJ on behalf of the SPRINT-MS Investigators. Response to Ibudilast treatment according to progressive multiple sclerosis disease phenotype. Annals of Clinical & Translational Neurology2021 January8(1)111-118.
    PubMed: PMC7818089

  • Robert A Bermel, Janel K Fedler, Peter Kaiser, Cindy Novalis, Jeff Schneebaum, Elizabeth A Klingner, Dawn Williams, Jon W Yankey, Dixie J Ecklund, Marianne Chase, Robert T Naismith, Eric C Klawiter, Andrew D Goodman, Christopher S Coffey and Robert J Fox Optical coherence tomography outcomes from SPRINT-MS, a multicenter, randomized, double-blind trial of ibudilast in progressive multiple sclerosis. Multiple Sclerosis Journal2020 Oct 15
    PubMed: 33054533

  • Fox RJ, Coffey CS, Conwit R, Cudkowicz ME, Gleason T, Goodman A, Klawiter EC, Matsuda K, McGovern M, Naismith RT, Ashokkumar A, Barnes J, Ecklund DJ, Klinger E, Koepp M, Long JD, Natarajan S, Thornell B, Yankey J, Bermel RA, Debbins JP, Huang X, Jagodnik P, Lowe MK, Nakamura K, Narayanan S, Sakaie KE, Thoomukuntla B, Zhou X, Krieger S, Alvarez E, Apperson M, Bashir K, Cohen BA, Coyle PK, Delgado S, Dewitt D, Flores A, Giesser BS, Goldman MD, Jubelt B, Lava N, Lynch SG, Moses H, Ontaneda D, Perumal JS, Racke M, Repobic P, Riler CS, Severson C, Shinnar S, Suski V, Weinstock-Guttman B, Yadav V, Zabeti A for the NN102/SPRINT-MS Trial Investigators Phase 2 Trial of Ibudilast in Progressive Multiple Sclerosis. New England Journal of Medicine2018 Aug 30379(9)846-855.
    PubMed: PMC6172944

  • Fox RJ, Coffey CS, Cudkowicz ME, Gleason T, Goodman A, Klawiter EC, Matsuda K, McGovern M, Conwit R, Naismith R, Ashokkumar A, Bermel R, Ecklund D, Koepp M, Long J, Natarajan S, Ramachandran S, Skaramagas T, Thornell B, Yankey J, Agius M, Bashir K, Cohen B, Coyle P, Delgado S, Dewitt D, Flores A, Giesser B, Goldman M, Jubelt B, Lava N, Lynch S, Miravalle A, Moses H, Ontaneda D, Perumal J, Racke M, Repovic P, Riley C, Severson C, Shinnar S, Suski V, Weinstock-Gutman B, Yadav V, Zabeti A. Design, rationale, and baseline characteristics of the randomized double-blind phase II clinical trial of ibudilast in progressive multiple sclerosis. Contemporary Clinical Trials201650166-177.
    PubMed: PMC5035622