MN-166 for ALS (COMBAT-ALS Trial)
Recruiting in Palo Alto (17 mi)
+21 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2 & 3
Recruiting
Sponsor: MediciNova
Prior Safety Data
Trial Summary
What is the purpose of this trial?A Phase 2b/3 multicenter, randomized, double-blind, placebo-controlled, parallel group study to evaluate the efficacy, safety and tolerability of MN-166 given to ALS participants for 12 months followed by a 6-month open-label extension phase.
Do I need to stop my current medications to join the trial?The trial does not specify that you need to stop all current medications. However, if you are using riluzole, you must be on a stable dose for at least 30 days before starting the study drug. If you are using edaravone, you should have completed at least 14 days of your initial treatment cycle before starting the study drug.
Is the drug MN-166 (Ibudilast) a promising treatment for ALS?MN-166 (Ibudilast) shows potential as a treatment for ALS because it may protect nerve cells and slow down the disease. It works by reducing harmful inflammation in the brain and spinal cord. Early studies suggest it could improve survival and quality of life for people with ALS.14589
What safety data is available for MN-166 (ibudilast) in ALS treatment?Safety data for MN-166 (ibudilast) in ALS treatment comes from an open-label trial where 35 participants received up to 100 mg/day for 36 weeks. 86% experienced at least one adverse event possibly related to the drug. 37% could not tolerate the full dose and required a reduction, while 31% discontinued due to adverse events. The study suggests that dose reductions and discontinuations due to adverse events are common at this dosage, indicating a need for further pharmacokinetic and dose-finding studies to better understand tolerability.23456
What data supports the idea that MN-166 for ALS is an effective drug?The available research shows that MN-166 (ibudilast) has potential as a treatment for ALS, as early-phase studies suggest it may improve survival outcomes and slow disease progression. However, a specific study found no significant reductions in markers of disease activity, and many participants experienced side effects, leading to dose reductions or discontinuation. Compared to other treatments like riluzole, which only modestly extends survival, MN-166's effectiveness is still uncertain and requires further research.12457
Eligibility Criteria
This trial is for adults aged 18-80 with ALS diagnosed within the last 18 months. Participants must have a certain level of lung function and be able to swallow pills, without severe liver issues or psychiatric disorders that could interfere with assessments. They shouldn't be on high-dose Vitamin B12 injections or involved in other studies recently.Inclusion Criteria
I have been diagnosed with ALS according to the El Escorial criteria.
Exclusion Criteria
My liver isn't working properly (high AST or ALT levels).
I do not have a psychiatric disorder or dementia that affects my ability to evaluate symptoms.
I have been treated with high dose Vitamin B12 injections recently.
I use a tracheostomy or need help breathing most of the day.
Participant Groups
The study tests MN-166 against a placebo over 12 months to see if it's effective and safe for ALS patients, followed by everyone getting MN-166 for another six months. It's randomized (participants are put into groups by chance) and double-blind (neither participants nor researchers know who gets what treatment).
2Treatment groups
Experimental Treatment
Placebo Group
Group I: MN-166Experimental Treatment1 Intervention
Subjects will take MN-166 10 mg capsules, up to 50 mg twice a day for 12 months.
Group II: placeboPlacebo Group1 Intervention
Subjects will take up to 5 matching placebo capsules twice a day for 12 months.
MN-166 is already approved in Japan for the following indications:
🇯🇵 Approved in Japan as Ibudilast for:
- Anti-inflammatory
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Hopital de L'Enfant-Jesus, CHU de Quebec-Universite LavalQuebec, Canada
Mayo Clinic FloridaJacksonville, FL
Mayo Clinic RochesterRochester, MN
University of California, IrvineOrange, CA
More Trial Locations
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Who is running the clinical trial?
MediciNovaLead Sponsor
References
Phase II screening trial of lithium carbonate in amyotrophic lateral sclerosis: examining a more efficient trial design. [2021]To use a historical placebo control design to determine whether lithium carbonate slows progression of amyotrophic lateral sclerosis (ALS).
The effects of dexpramipexole (KNS-760704) in individuals with amyotrophic lateral sclerosis. [2022]Amyotrophic lateral sclerosis (ALS) is characterized by upper and lower motor neuron dysfunction and loss, rapidly progressive muscle weakness, wasting and death. Many factors, including mitochondrial dysfunction, may contribute to ALS pathogenesis. Riluzole, which has shown only modest benefits in a measure of survival time without demonstrated effects on muscle strength or function, is the only approved treatment for ALS. We tested the putative mitochondrial modulator dexpramipexole (KNS-760704; (6R)-4,5,6,7-tetrahydro-N6-propyl-2,6-benzothiazole-diamine) in subjects with ALS in a two-part, double-blind safety and tolerability study, with a preliminary assessment of its effects on functional decline and mortality. In part 1, the effects of dexpramipexole (50, 150 or 300 mg d(-1)) versus placebo were assessed over 12 weeks. In part 2, after a 4-week, single-blind placebo washout, continuing subjects were re-randomized to dexpramipexole at 50 mg d(-1) or 300 mg d(-1) as double-blind active treatment for 24 weeks. Dexpramipexole was safe and well tolerated. Trends showing a dose-dependent attenuation of the slope of decline of the ALS Functional Rating Scale-Revised (ALSFRS-R) in part 1 and a statistically significant (P = 0.046) difference between groups in a joint rank test of change from baseline in ALSFRS-R and mortality in part 2 strongly support further testing of dexpramipexole in ALS.
Safety and efficacy of edaravone compared to historical controls in patients with amyotrophic lateral sclerosis from North-Eastern Italy. [2020]To test efficacy and tolerability of edaravone in patients with amyotrophic lateral sclerosis (ALS) originating from North-Eastern Italy.
Ibudilast (MN-166) in amyotrophic lateral sclerosis- an open label, safety and pharmacodynamic trial. [2023]Ibudilast (MN-166) is an inhibitor of macrophage migration inhibitory factor (MIF) and phosphodiesterases 3,4,10 and 11 (Gibson et al., 2006; Cho et al., 2010). Ibudilast attenuates CNS microglial activation and secretion of pro-inflammatory cytokines (Fujimoto et al., 1999; Cho et al., 2010). In vitro evidence suggests that ibudilast is neuroprotective by suppressing neuronal cell death induced by microglial activation. People with ALS have increased microglial activation measured by [11C]PBR28-PET in the motor cortices. The primary objective is to determine the impact of ibudilast on reducing glial activation and neuroaxonal loss in ALS, measured by PBR28-PET and serum Neurofilament light (NfL). The secondary objectives included determining safety and tolerability of ibudilast high dosage (up to 100 mg/day) over 36 weeks. In this open label trial, 35 eligible ALS participants underwent ibudilast treatment up to 100 mg/day for 36 weeks. Of these, 30 participants were enrolled in the main study cohort and were included in biomarker, safety and tolerability analyses. Five additional participants were enrolled in the expanded access arm, who did not meet imaging eligibility criteria and were included in the safety and tolerability analyses. The primary endpoints were median change from baseline in (a) PBR28-PET uptake in primary motor cortices, measured by standard uptake value ratio (SUVR) over 12-24 weeks and (b) serum NfL over 36-40 weeks. The secondary safety and tolerability endpoints were collected through Week 40. The baseline median (range) of PBR28-PET SUVR was 1.033 (0.847, 1.170) and NfL was 60.3 (33.1, 219.3) pg/ml. Participants who completed both pre and post-treatment scans had PBR28-PET SUVR median(range) change from baseline of 0.002 (-0.184, 0.156) , P = 0.5 (n = 22). The median(range) NfL change from baseline was 0.4 pg/ml (-1.8, 17.5), P = 0.2 (n = 10 participants). 30(86%) participants experienced at least one, possibly study drug related adverse event. 13(37%) participants could not tolerate 100 mg/day and underwent dose reduction to 60-80 mg/day and 11(31%) participants discontinued study drug early due to drug related adverse events. The study concludes that following treatment with ibudilast up to 100 mg/day in ALS participants, there were no significant reductions in (a) motor cortical glial activation measured by PBR28-PET SUVR over 12-24 weeks or (b) CNS neuroaxonal loss, measured by serum NfL over 36-40 weeks. Dose reductions and discontinuations due to treatment emergent adverse events were common at this dosage in ALS participants. Future pharmacokinetic and dose-finding studies of ibudilast would help better understand tolerability and target engagement in ALS.
MN-166 (ibudilast) in amyotrophic lateral sclerosis in a Phase IIb/III study: COMBAT-ALS study design. [2022]Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with motor neuron loss as a defining feature. Despite significant effort, therapeutic breakthroughs have been modest. MN-166 (ibudilast) has demonstrated neuroprotective action by various mechanisms: inhibition of proinflammatory cytokines and macrophage migration inhibitory factor, phosphodiesterase inhibition, and attenuation of glial cell activation in models of ALS. Early-phase studies suggest that MN-166 may improve survival outcomes and slow disease progression in patients with ALS. This article describes the rationale and design of COMBAT-ALS, an ongoing randomized, double-blind, placebo-controlled, multicenter Phase IIb/III study in ALS. This study is designed to evaluate the pharmacokinetics, safety and tolerability and assess the efficacy of MN-166 on function, muscle strength, quality of life and survival in ALS.
Analysis of the US Safety Data for Edaravone (Radicava®) From the Third Year After Launch. [2022]Label="BACKGROUND" NlmCategory="BACKGROUND">Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neuromuscular disease with no curative therapies. Edaravone (Radicava®) (Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan), approved in the United States (US) for ALS in adults in 2017, was shown in a clinical trial to slow the rate of physical functional decline in ALS and is administered intravenously. The aim of this paper is to summarize the observed safety profile from real-world patient use during the first 3 years of edaravone availability in the US.
Motor Neuron Disease Systematic Multi-Arm Adaptive Randomised Trial (MND-SMART): a multi-arm, multi-stage, adaptive, platform, phase III randomised, double-blind, placebo-controlled trial of repurposed drugs in motor neuron disease. [2023]Motor neuron disease (MND) is a rapidly fatal neurodegenerative disease. Despite decades of research and clinical trials there remains no cure and only one globally approved drug, riluzole, which prolongs survival by 2-3 months. Recent improved mechanistic understanding of MND heralds a new translational era with many potential targets being identified that are ripe for clinical trials. Motor Neuron Disease Systematic Multi-Arm Adaptive Randomised Trial (MND-SMART) aims to evaluate the efficacy of drugs efficiently and definitively in a multi-arm, multi-stage, adaptive trial. The first two drugs selected for evaluation in MND-SMART are trazodone and memantine.
New developments and opportunities in drugs being trialed for amyotrophic lateral sclerosis from 2020 to 2022. [2022]Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that primarily affects motor neurons in the brain and spinal cord. In the recent past, there have been just two drugs approved for treatment, riluzole and edaravone, which only prolong survival by a few months. However, there are many novel experimental drugs in development. In this review, we summarize 53 new drugs that have been evaluated in clinical trials from 2020 to 2022, which we have classified into eight mechanistic groups (anti-apoptotic, anti-inflammatory, anti-excitotoxicity, regulated integrated stress response, neurotrophic factors and neuroprotection, anti-aggregation, gene therapy and other). Six were tested in phase 1 studies, 31 were in phase 2 studies, three failed in phase 3 studies and stopped further development, and the remaining 13 drugs were being tested in phase 3 studies, including methylcobalamin, masitinib, MN-166, verdiperstat, memantine, AMX0035, trazodone, CNM-Au8, pridopidine, SLS-005, IONN363, tofersen, and reldesemtiv. Among them, five drugs, including methylcobalamin, masitinib, AMX0035, CNM-Au8, and tofersen, have shown potent therapeutic effects in clinical trials. Recently, AMX0035 has been the third medicine approved by the FDA for the treatment of ALS after riluzole and edaravone.
Statistical analysis plan for the motor neuron disease systematic multi-arm adaptive randomised trial (MND-SMART). [2023]MND-SMART is a platform, multi-arm, multi-stage, multi-centre, randomised controlled trial recruiting people with motor neuron disease. Initially, the treatments memantine and trazodone will each be compared against placebo, but other investigational treatments will be introduced into the trial later. The co-primary outcomes are the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALS-FRS-R) functional outcome, which is assessed longitudinally, and overall survival.