Author Topic: Phase 2 trial of ibudilast, potential treatment for progressive MS  (Read 279 times)

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Offline agate

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From the Rocky Mountain MS Center News, June 30, 2014:

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New study will explore potential treatment for progressive MS
 
At this time, there is a significant gap in available treatment options for people living with progressive MS. The good news is that researchers are paying more attention to this critical area of research. In May, we told you about research being conducted on statins and how the cholesterol-lowering drugs could impact progressive MS. Now, the Rocky Mountain MS Center MS Center at Anschutz Medical Center—along with other national sites—is beginning a new study to test a drug called ibudilast.

This new study will test the safety, tolerability and activity of ibudilast in people with primary and secondary progressive multiple sclerosis. Researchers are currently looking for participants to take part in the study.

"We have an opportunity, by studying this novel molecule, to add to the growing body of research, and potentially have an impact, on progressive disease," said Dr. John Corboy.

This study is being conducted at 28 sites across the country through a consortium called NeuroNEXT (The Network for Excellence in Neuroscience Clinical Trials). Participation in the study is not limited to Colorado residents – study sites are located nationwide. NeuroNEXT studies are funded by the National Institutes of Health (NIH) and are designed to create increased efficiency in neurological research trials. The University of Colorado Denver is one of 25 NeuroNEXT sites.

More about ibudilast

Ibudilast is an oral medication that is approved in Japan for post-stroke use and asthma. In a 2010 Dutch study on relapsing forms of MS, ibudilast showed no beneficial effect on newly active lesions and relapses. The preliminary evidence, however, suggested that ibudilast may act in a neuroprotective way. Neuroprotection simply means that it protects neurons that have been damaged, and therefore helps preserve brain function. This is likely because ibuldilast is a phosphodiesterase (PDE) inhibitor, which means it influences inflammation and neurodegeneration.

Study details

People with primary or secondary progressive multiple sclerosis are eligible for the study only if they are not currently on a disease modifying treatment (DMT), or are currently taking Copaxone, Avonex, Rebif or any other formulation of an Interferon Beta. The study will be stratified by disease status and by current use of a DMT.
Ibudilast will be administered to study participants twice daily over a 96 week period. The study will consist of a screening phase and a treatment phase, as well as a follow up visit. After the screening phase, participants who meet the study criteria will be assigned to one of two treatment groups: taking 100 mg of ibudilast per day or a matching placebo.

Participating in the study


Researchers nationwide are recruiting participants for the study. If you are interested in participating in the ibudilast study or learning more about it, please click here.
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Offline agate

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(AAN) Phase II trial of ibudilast in progressive MS
« Reply #1 on: April 27, 2015, 02:46:10 pm »
Presented at the annual AAN conference in Washington, DC:

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[P7.214] NN 102/SPRINT-MS Phase II Trial of Ibudilast in Progressive MS: Baseline Characteristics


Robert Fox,1Christopher Coffey,2Merit Cudkowicz,3Trevis Gleason,4Andrew Goodman,5Eric Klawiter,3Kazuko Matsuda,6Michelle McGovern,3Elizabeth McNeil,7Robert Naismith,8Jon Yankey2

1Cleveland, OH, USA, 2Iowa City, IA, USA, 3Boston, MA, USA, 4Seattle, WA, USA, 5Rochester, NY, USA, 6La Jolla, CA, USA, 7Bethesda, MD, USA, 8Saint Louis, MO, USA.

OBJECTIVE:

To report baseline characteristics of subjects enrolled in a phase II trial of ibudilast in progressive MS (PMS).

BACKGROUND:

Approved therapies for relapsing remitting MS lack proven efficacy in PMS. The optimal outcome metric for phase II trials in PMS is unknown. Ideally, a phase II trial in PMS would both evaluate a potential therapy and establish outcome metrics.

DESIGN/METHODS:

NN 102/SPRINT-MS is a phase II trial of ibudilast in primary and secondary PMS utilizing the NINDS-sponsored NeuroNEXT clinical trial network. The trial will evaluate the safety, tolerability, and activity of ibudilast and directly compare imaging outcome metrics: whole brain atrophy, magnetization transfer imaging, diffusion tensor imaging, optical coherence tomography, and cortical atrophy. Approximately 250 subjects will be randomized at 28 US sites, randomized 1:1 to ibudilast 100mg/d or placebo, and followed over 96 weeks.

RESULTS:

As of October 2014, 225 subjects were enrolled and 164 randomized. Of those randomized, mean age = 55.7 yrs (SD 7.3; range 31-65); 54% female; 93% white; 4.3% Latino; mean EDSS = 5.40 (SD 1.1; range 3 - 7), mean 25FW time = 16.1 seconds (SD 19.4; range 4.05 - 180), and mean 9HPT time = 32.9 seconds (SD 16.5; range 16.3 - 111.3) (dominant) and 42.3 seconds (SD 46.3; range 17.5 - 300) (non-dominant). Enrollment is projected to be completed by January 2015. Baseline characteristics of the fully-enrolled study will be presented.

CONCLUSIONS:

The NN102/SPRINT-MS will evaluate the activity of ibudilast and directly compare five imaging outcome metrics to help improve the conduct of phase II trials in PMS. To date, baseline characteristics are typical of the PMS population.

_____________________
Study Supported by:
Support by National Institute of Health (U01NS082329), National Multiple Sclerosis Society (RG-5184-A-6) and Medicinova

Category - MS and CNS Inflammatory Disease: Clinical Science

Session: P7: Poster Session VII: MS and CNS Inflammatory Diseases: Clinical Trials (2:00 PM-6:30 PM)
Date/Time: Thursday, April 23, 2015 - 2:00 pm
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Offline agate

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An update from the National MS Society, May 12, 2015:

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National MS Society Joins with the National Institutes of Health to Fund a Major Trial of a Re-Purposed Therapy in Progressive MS - UPDATED


Updated, May 12, 2015: This study has completed enrollment. According to the listing on clinicaltrials.gov, the study should complete data collection by the end of May 2017.

Investigators at the Cleveland Clinic Foundation are launching a phase II clinical trial of ibudilast (MN-166, MediciNova, Inc.), an oral anti-inflammatory agent, in 250 people with progressive forms of MS. The study is principally funded by NeuroNEXT Network, a clinical trials initiative of the National Institutes of Health, with additional support by MediciNova, the company that will supply ibudilast. The National MS Society actively advocated for this uniquely collaborative trial, and is also providing funding support because it aligns with the Society’s strategic focus on progressive MS, and may answer important questions about the best ways to measure the benefits of therapies aimed at protecting the nervous system from MS. The trial is being conducted at 28 sites across the U.S. under the leadership of Principal Investigator Robert Fox, M.D., M.S., FAAN, Staff Neurologist at the Mellen Center for Multiple Sclerosis at Cleveland Clinic.

“There is a significant, unmet need for treatments that can benefit people with progressive forms of MS,” said Timothy Coetzee, PhD, Chief Research Officer of the National MS Society. “This clinical trial of ibudilast will provide important information on a potential way to stop MS damage, as well as how to measure treatment benefits, and aligns well with the Society’s research agenda for stopping MS progression.” This could lead to shorter, more effective trials and the potential for getting new therapies to people with MS faster.

Background:

Ibudilast inhibits an enzyme called phosphodiesterase, resulting in suppression of inflammation. While considered a “New Molecular Entity” in the United States and Europe, ibudilast is marketed in Japan and Korea to treat cerebrovascular disorders and asthma. It is being investigated in the U.S. for its potential to treat drug addiction.

In a previous study, ibudilast did not reduce relapses or MRI-observed new lesions in a phase II trial of 292 people with relapsing MS. However, some evidence that this agent could protect the nervous system from damage (neuroprotection) was observed. Frederick Barkhof, MD, PhD (VU University Medical Center, Amsterdam) and colleagues published these findings in Neurology (2010;74:1033).

This Study:

Dr. Fox and his colleagues at Cleveland Clinic [are] collaborating with co-investigators at 28 academic medical centers in the NeuroNEXT Network. The trial is expected to require approximately three years for enrollment, treatment, and data analyses. The trial is recruiting individuals who have either primary-progressive MS or secondary-progressive MS and who meet specific entrance criteria. Like the Society’s previous investment in a clinical trial of estriol, this trial is an example of how the Society can join with multiple partners to facilitate testing of an “on the shelf” therapy in people with MS.
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Offline agate

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From Multiple Sclerosis News Today, June 15, 2015:

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MediciNova announces update on Phase 2b trial of MN-166 (Ibudilast) involving 255 progressive MS patients

MediciNova, Inc., a biopharmaceutical company focused on acquiring and developing novel, small-molecule therapeutics for the treatment of diseases with unmet medical needs, recently announced that the ongoing clinical trial of MN-166 (ibudilast) in patients with progressive multiple sclerosis (progressive MS) has finished the randomization of 255 patients, exceeding the initial goal of 250 patients.

The National Institute of Neurological Disorders and Stroke (NINDS) aims to conduct an interim analysis of the drug efficacy in the fall of 2016, once half of the patients have completed the treatment over 96 weeks.

Yuichi Iwaki, MD, PhD, President and Chief Executive Officer of MediciNova, Inc., commented in a recent press release, “We are very pleased to have exceeded the enrollment target in this important study. The unmet medical need for progressive MS patients is extremely high as there is no treatment approved for long-term use for these patients. We look forward to providing further updates as the study progresses.”

MN-166 is a first-in-class, orally bioavailable, small molecule glial attenuator that suppresses pro-inflammatory cytokines IL-1ß, TNF-a, and IL-6, and may upregulate the anti-inflammatory cytokine IL-10.

The SPRINT-MS is a Phase 2 Secondary and Primary Progressive Ibudilast NeuroNEXT trial in patients with Multiple Sclerosis designed to evaluate the tolerability, safety, and efficacy of MN-166 (ibudilast) given twice per day to patients with primary or secondary progressive multiple sclerosis (PPMS or SPMS). It involves 28 clinical sites across the United States.

Patients were randomized to receive an inactive control (placebo) or MN-166 (ibudilast) 100 mg/day (50 mg twice daily). For the remainder of the study, patients may be either untreated with long-term disease modifying therapy (DMT) or may continue either glatiramer acetate (GA) or interferon beta (IFNβ-1a or IFNβ-1b) treatment.

The trial involves a controlled randomization therapy status (IFN/GA verus. no DMT) and disease status (PPMS versus SPMS).

The study primary endpoints are to evaluate the activity of the drug in comparison to the placebo over a period of time of 96 weeks. This will be assessed with magnetic resonance imaging (MRI) using brain parenchymal fraction (BPF). The other primary endpoint involves the assessment of the drug safety and tolerability versus the placebo in with PPMS or SPMS patients. The study secondary endpoints involve imaging analyses of brain and retinal tissue integrity, cortical atrophy disability, cognitive impairment, neuropathic pain and quality-of-life. The study will also include an exploratory analysis of pharmacokinetic and biomarker.
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Offline agate

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From Multiple Sclerosis News Today, March 24, 2016:

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Potential Progressive MS Treatment, Ibudilast, Approved for Fast Track Development by FDA

  Carolina Henriques

MediciNova, Inc., announced that MN-166 (ibudilast) has been approved for “fast track” development by the U.S. Food and Drug Administration (FDA) as a potential treatment for progressive multiple sclerosis (MS). Progressive MS includes both the primary progressive (PPMS) and secondary progressive (SPMS) forms of the disease.

MediciNova’s MN-166 was licensed from Kyorin Pharmaceuticals for its potential in treating relapsing-remitting MS (RRMS). MN-166 is a first-in-class, orally bioavailable, small-molecule phosphodiesterase (PDE) -4 and -10 inhibitor and a macrophage migration inhibitory factor (MIF) inhibitor that works by suppressing pro-inflammatory cytokines and promoting neurotrophic factors. It reduces activated glial cells, which play a significant role in a number of neurological conditions.

Ibudilast’s anti-neuroinflammatory and neuroprotective actions have been demonstrated in preclinical and clinical studies, that were the basis for investigating its ... utility in neurodegenerative diseases like progressive MS and amyotrophic lateral sclerosis, and in substance abuse and chronic neuropathic pain.

“We are very pleased that MN-166 has received Fast Track Designation for progressive MS and believe this validates its potential to address unmet medical needs for this serious disease. We look forward to providing further updates from our ongoing clinical trial in progressive MS,” Yuichi Iwaki, MD, PhD, MediciNova’s president and chief executive officer, said in a press release.

...
Current MS therapies address the inflammatory response in RRMS, but are of limited or no benefit regarding neurodegeneration or brain tissue repair.

The FDA’s Fast Track designation is awarded to speed the development and review of drugs with the potential to address unmet medical needs in serious or life-threatening diseases.
MS Speaks--online for 13 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010.