Design, rationale, and baseline characteristics of the randomized double-blind phase II clinical trial of ibudilast in progressive multiple sclerosis

Robert J. Fox, Christopher S. Coffey, Merit E. Cudkowicz, Trevis Gleason, Andrew Goodman, Eric C. Klawiter, Kazuko Matsuda, Michelle McGovern, Robin Conwit, Robert Naismith, Akshata Ashokkumar, Robert Bermel, Dixie Ecklund, Maxine Koepp, Jeffrey Long, Sneha Natarajan, Srividya Ramachandran, Thomai Skaramagas, Brenda Thornell, Jon Yankey & 25 others Mark Agius, Khurram Bashir, Bruce Cohen, Patricia Coyle, Silvia Delgado, Dana Dewitt, Angela Flores, Barbara Giesser, Myla Goldman, Burk Jubelt, Neil Lava, Sharon Lynch, Augusto Miravalle, Harold Moses, Daniel Ontaneda, Jai Perumal, Michael Racke, Pavle Repovic, Claire Riley, Christopher Severson, Shlomo Shinnar, Valerie Suski, Bianca Weinstock-Gutman, Vijayshree Yadav, Aram Zabeti

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Background Primary and secondary progressive multiple sclerosis (MS), collectively called progressive multiple sclerosis (PMS), is characterized by gradual progression of disability. The current anti-inflammatory treatments for MS have little or no efficacy in PMS in the absence of obvious active inflammation. Optimal biomarkers for phase II PMS trials is unknown. Ibudilast is an inhibitor of macrophage migration inhibitor factor and phosphodiesterases-4 and − 10 and exhibits possible neuroprotective properties. The goals of SPRINT-MS study are to evaluate the safety and efficacy of ibudilast in PMS and to directly compare several imaging metrics for utility in PMS trials. Methods SPRINT-MS is a randomized, placebo-controlled, phase II trial of ibudilast in patients with PMS. Eligible subjects were randomized 1:1 to receive either ibudilast (100 mg/day) or placebo for 96 weeks. Imaging is conducted every 24 weeks for whole brain atrophy, magnetization transfer ratio, diffusion tensor imaging, cortical brain atrophy, and retinal nerve fiber layer thickness. Clinical outcomes include neurologic disability and patient reported quality of life. Safety assessments include laboratory testing, electrocardiography, and suicidality screening. Results A total of 331 subjects were enrolled, of which 255 were randomized onto active study treatment. Randomized subjects were 53.7% female and mean age 55.7 (SD 7.3) years. The last subject is projected to complete the study in May 2017. Conclusion SPRINT-MS is designed to evaluate the safety and efficacy of ibudilast as a treatment for PMS while simultaneously validating five different imaging biomarkers as outcome metrics for use in future phase II proof-of-concept PMS trials.

Original languageEnglish (US)
Pages (from-to)166-177
Number of pages12
JournalContemporary Clinical Trials
Volume50
DOIs
StatePublished - Sep 1 2016

Fingerprint

Phase II Clinical Trials
Multiple Sclerosis
Chronic Progressive Multiple Sclerosis
Safety
Atrophy
ibudilast
Biomarkers
Placebos
Phosphodiesterase 4 Inhibitors
Diffusion Tensor Imaging
Brain
Nerve Fibers
Nervous System
Electrocardiography
Anti-Inflammatory Agents
Therapeutics
Macrophages

Keywords

  • Clinical trial
  • Ibudilast
  • Magnetic resonance imaging
  • Progressive multiple sclerosis

ASJC Scopus subject areas

  • Medicine(all)
  • Pharmacology (medical)

Cite this

Design, rationale, and baseline characteristics of the randomized double-blind phase II clinical trial of ibudilast in progressive multiple sclerosis. / Fox, Robert J.; Coffey, Christopher S.; Cudkowicz, Merit E.; Gleason, Trevis; Goodman, Andrew; Klawiter, Eric C.; Matsuda, Kazuko; McGovern, Michelle; Conwit, Robin; Naismith, Robert; Ashokkumar, Akshata; Bermel, Robert; Ecklund, Dixie; Koepp, Maxine; Long, Jeffrey; Natarajan, Sneha; Ramachandran, Srividya; Skaramagas, Thomai; Thornell, Brenda; Yankey, Jon; Agius, Mark; Bashir, Khurram; Cohen, Bruce; Coyle, Patricia; Delgado, Silvia; Dewitt, Dana; Flores, Angela; Giesser, Barbara; Goldman, Myla; Jubelt, Burk; Lava, Neil; Lynch, Sharon; Miravalle, Augusto; Moses, Harold; Ontaneda, Daniel; Perumal, Jai; Racke, Michael; Repovic, Pavle; Riley, Claire; Severson, Christopher; Shinnar, Shlomo; Suski, Valerie; Weinstock-Gutman, Bianca; Yadav, Vijayshree; Zabeti, Aram.

In: Contemporary Clinical Trials, Vol. 50, 01.09.2016, p. 166-177.

Research output: Contribution to journalArticle

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 2016, 'Design, rationale, and baseline characteristics of the randomized double-blind phase II clinical trial of ibudilast in progressive multiple sclerosis', Contemporary Clinical Trials, vol. 50, pp. 166-177. https://doi.org/10.1016/j.cct.2016.08.009
Fox, Robert J. ; Coffey, Christopher S. ; Cudkowicz, Merit E. ; Gleason, Trevis ; Goodman, Andrew ; Klawiter, Eric C. ; Matsuda, Kazuko ; McGovern, Michelle ; Conwit, Robin ; Naismith, Robert ; Ashokkumar, Akshata ; Bermel, Robert ; Ecklund, Dixie ; Koepp, Maxine ; Long, Jeffrey ; Natarajan, Sneha ; Ramachandran, Srividya ; Skaramagas, Thomai ; Thornell, Brenda ; Yankey, Jon ; Agius, Mark ; Bashir, Khurram ; Cohen, Bruce ; Coyle, Patricia ; Delgado, Silvia ; Dewitt, Dana ; Flores, Angela ; Giesser, Barbara ; Goldman, Myla ; Jubelt, Burk ; Lava, Neil ; Lynch, Sharon ; Miravalle, Augusto ; Moses, Harold ; Ontaneda, Daniel ; Perumal, Jai ; Racke, Michael ; Repovic, Pavle ; Riley, Claire ; Severson, Christopher ; Shinnar, Shlomo ; Suski, Valerie ; Weinstock-Gutman, Bianca ; Yadav, Vijayshree ; Zabeti, Aram. / Design, rationale, and baseline characteristics of the randomized double-blind phase II clinical trial of ibudilast in progressive multiple sclerosis. In: Contemporary Clinical Trials. 2016 ; Vol. 50. pp. 166-177.
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abstract = "Background Primary and secondary progressive multiple sclerosis (MS), collectively called progressive multiple sclerosis (PMS), is characterized by gradual progression of disability. The current anti-inflammatory treatments for MS have little or no efficacy in PMS in the absence of obvious active inflammation. Optimal biomarkers for phase II PMS trials is unknown. Ibudilast is an inhibitor of macrophage migration inhibitor factor and phosphodiesterases-4 and − 10 and exhibits possible neuroprotective properties. The goals of SPRINT-MS study are to evaluate the safety and efficacy of ibudilast in PMS and to directly compare several imaging metrics for utility in PMS trials. Methods SPRINT-MS is a randomized, placebo-controlled, phase II trial of ibudilast in patients with PMS. Eligible subjects were randomized 1:1 to receive either ibudilast (100 mg/day) or placebo for 96 weeks. Imaging is conducted every 24 weeks for whole brain atrophy, magnetization transfer ratio, diffusion tensor imaging, cortical brain atrophy, and retinal nerve fiber layer thickness. Clinical outcomes include neurologic disability and patient reported quality of life. Safety assessments include laboratory testing, electrocardiography, and suicidality screening. Results A total of 331 subjects were enrolled, of which 255 were randomized onto active study treatment. Randomized subjects were 53.7{\%} female and mean age 55.7 (SD 7.3) years. The last subject is projected to complete the study in May 2017. Conclusion SPRINT-MS is designed to evaluate the safety and efficacy of ibudilast as a treatment for PMS while simultaneously validating five different imaging biomarkers as outcome metrics for use in future phase II proof-of-concept PMS trials.",
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T1 - Design, rationale, and baseline characteristics of the randomized double-blind phase II clinical trial of ibudilast in progressive multiple sclerosis

AU - Fox, Robert J.

AU - Coffey, Christopher S.

AU - Cudkowicz, Merit E.

AU - Gleason, Trevis

AU - Goodman, Andrew

AU - Klawiter, Eric C.

AU - Matsuda, Kazuko

AU - McGovern, Michelle

AU - Conwit, Robin

AU - Naismith, Robert

AU - Ashokkumar, Akshata

AU - Bermel, Robert

AU - Ecklund, Dixie

AU - Koepp, Maxine

AU - Long, Jeffrey

AU - Natarajan, Sneha

AU - Ramachandran, Srividya

AU - Skaramagas, Thomai

AU - Thornell, Brenda

AU - Yankey, Jon

AU - Agius, Mark

AU - Bashir, Khurram

AU - Cohen, Bruce

AU - Coyle, Patricia

AU - Delgado, Silvia

AU - Dewitt, Dana

AU - Flores, Angela

AU - Giesser, Barbara

AU - Goldman, Myla

AU - Jubelt, Burk

AU - Lava, Neil

AU - Lynch, Sharon

AU - Miravalle, Augusto

AU - Moses, Harold

AU - Ontaneda, Daniel

AU - Perumal, Jai

AU - Racke, Michael

AU - Repovic, Pavle

AU - Riley, Claire

AU - Severson, Christopher

AU - Shinnar, Shlomo

AU - Suski, Valerie

AU - Weinstock-Gutman, Bianca

AU - Yadav, Vijayshree

AU - Zabeti, Aram

PY - 2016/9/1

Y1 - 2016/9/1

N2 - Background Primary and secondary progressive multiple sclerosis (MS), collectively called progressive multiple sclerosis (PMS), is characterized by gradual progression of disability. The current anti-inflammatory treatments for MS have little or no efficacy in PMS in the absence of obvious active inflammation. Optimal biomarkers for phase II PMS trials is unknown. Ibudilast is an inhibitor of macrophage migration inhibitor factor and phosphodiesterases-4 and − 10 and exhibits possible neuroprotective properties. The goals of SPRINT-MS study are to evaluate the safety and efficacy of ibudilast in PMS and to directly compare several imaging metrics for utility in PMS trials. Methods SPRINT-MS is a randomized, placebo-controlled, phase II trial of ibudilast in patients with PMS. Eligible subjects were randomized 1:1 to receive either ibudilast (100 mg/day) or placebo for 96 weeks. Imaging is conducted every 24 weeks for whole brain atrophy, magnetization transfer ratio, diffusion tensor imaging, cortical brain atrophy, and retinal nerve fiber layer thickness. Clinical outcomes include neurologic disability and patient reported quality of life. Safety assessments include laboratory testing, electrocardiography, and suicidality screening. Results A total of 331 subjects were enrolled, of which 255 were randomized onto active study treatment. Randomized subjects were 53.7% female and mean age 55.7 (SD 7.3) years. The last subject is projected to complete the study in May 2017. Conclusion SPRINT-MS is designed to evaluate the safety and efficacy of ibudilast as a treatment for PMS while simultaneously validating five different imaging biomarkers as outcome metrics for use in future phase II proof-of-concept PMS trials.

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KW - Clinical trial

KW - Ibudilast

KW - Magnetic resonance imaging

KW - Progressive multiple sclerosis

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