TY - JOUR
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
N1 - Funding Information:
This study was funded by the NINDS ( U01NS082329 ) and NMSS ( RG 4778-A-6 ). Ibudilast study drug was provided at no cost by MediciNova Inc. The NeuroNEXT Network is supported by the NINDS (Central Coordinating Center: U01NS077179, Data Coordinating Center: U01NS077352). We thank Dr. Elizabeth McNeil, the former program manager at NINDS, for her steady support through the trial development and start-up process. This study was made possible by the dedication and support of people with MS who volunteered to participate as well as their families and friends who support their involvement in this study.
Funding Information:
The clinical trial is a collaborative study conducted by the Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT). Started in 2011, NeuroNEXT is an initiative of the National Institute of Neurological Disorders and Stroke (NINDS) designed to accelerate development of therapies for neurological diseases through partnerships with academic institutions, non-profit organizations, and industry. The core of NeuroNEXT comprises a Clinical Coordinating Center (CCC, which is located at the Massachusetts General Hospital, Boston, MA), a Data Coordinating Center (DCC, which is located at the University of Iowa, Iowa City, IA), and 25 academic medical centers across the US. Central to the function of NeuroNEXT is external peer-review to ensure high quality scientific rigor; centralized ethics oversight, which is provided through the Central Institutional Review Board (CIRB) at Massachusetts General Hospital; a single master clinical trial agreement for each participating clinical site, through which all NeuroNEXT trials at that site are contracted; and operational support by the NINDS. Details about NeuroNEXT structure have been published previously [28] . Funding for the SPRINT-MS trial is primarily through a competitive peer-reviewed grant issued by the NINDS, with additional funding provided by the National MS Society and Medicinova, which holds intellectual property rights to ibudilast.
Publisher Copyright:
© 2016 Elsevier Inc.
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.
AB - 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.
KW - Clinical trial
KW - Ibudilast
KW - Magnetic resonance imaging
KW - Progressive multiple sclerosis
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UR - http://www.scopus.com/inward/citedby.url?scp=84984783725&partnerID=8YFLogxK
U2 - 10.1016/j.cct.2016.08.009
DO - 10.1016/j.cct.2016.08.009
M3 - Article
C2 - 27521810
AN - SCOPUS:84984783725
SN - 1551-7144
VL - 50
SP - 166
EP - 177
JO - Contemporary Clinical Trials
JF - Contemporary Clinical Trials
ER -