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Amyotrophic Lateral SclerosisPhase 1/2NCT02714036

A Biomarker Study to Evaluate MN-166 in Subjects With Amyotrophic Literal Sclerosis (ALS)

A Phase 1/2 study testing ibudilast in people with Amyotrophic Lateral Sclerosis, run by MediciNova at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a multi-center, open-label study of MN-166 (ibudilast) in subjects with ALS. To be eligible subjects must meet the El Escorial criteria of possible, laboratory-supported probable, probable, or definite criteria for a diagnosis of ALS. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Amyotrophic Lateral Sclerosis
What is being tested?
ibudilast
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
2 sitesUnited States
Study dates
6 May 2016to 30 Jun 2020
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subjects must be diagnosed as having possible, probable, probable-laboratory supported, or definite ALS, either sporadic or familial according to modified El Escorial criteria.
  • Age 18 or above, able to provide informed consent, and safely comply with study procedures.
  • Vital capacity (VC) of at least 50% predicted value for gender, height and age at screening visit, or in the opinion of the study physician, able to safely tolerate study procedures. (Not applicable to flexible arm)
  • Subject must be able to swallow oral medication at the Baseline Visit and expected to be able to swallow the capsules throughout the course of the study.
  • Subject must not have taken riluzole for at least 30 days or be on a stable dose of riluzole for at least 30 days, prior to screening (riluzole-naïve participants are permitted in the study). (Not applicable to flexible arm)
  • Women must not be able to become pregnant (e.g. post-menopausal, surgically sterile, or using adequate birth control) for the duration of the study and 3 months after study completion.
Show all 10Show fewer
  • Males should practice contraception for the duration of the study and 3 months after completion.
  • Ability to safely lie flat for 90 min for PET procedures in the opinion of the study physician. (Not applicable to flexible arm)
  • High or mixed affinity to bind TSPO protein (Ala/Ala or Ala/Thr) (not applicable to flexible arm).
  • Upper motor Neuron Burden (UMNB) Score ≥25 (out of 45) at screening visit. (Not applicable to flexible arm)

Who cannot join

  • Abnormal liver function defined as AST and/or ALT > 3 times the upper limit of the normal.
  • Renal insufficiency as defined by a serum creatinine > 1.5 times the upper limit of normal.
  • The presence of unstable psychiatric disease, cognitive impairment, or dementia that would impair ability of the participant to provide informed consent, according to PI judgment.
  • Clinically significant unstable medical condition (other than ALS) that would pose a risk to the participant if they were to participate in the study.
  • History of HIV, clinically significant chronic hepatitis, or other active infection.
  • Active inflammatory condition of autoimmune disorder (Not applicable to flexible arm)
Show all 18Show fewer
  • Females must not be lactating or pregnant.
  • Active participation in another ALS clinical trial or exposure to an off-label ALS experimental treatment within 30 days of the Baseline Visit (Not applicable to flexible arm)
  • Exposure to immunomodulatory medications within 30 days of the Baseline Visit. (Not applicable to flexible arm)
  • Any contraindication to undergo MRI studies such as
  • History of a cardiac pacemaker or pacemaker wires
  • Metallic particles in the body
  • Vascular clips in the head
  • Prosthetic heart valves
  • Claustrophobia (Not applicable to flexible arm)
  • Radiation exposure that exceeds the site's current guidelines (Not applicable to flexible arm)
  • EKG finding of QTc prolongation > 450 msec for males and > 470 msec for females at screening or baseline.
  • Not on any prohibitive medication or known QT prolonging medication:

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • South Shore Neurologic Associates, P.C.

    Patchogue, New York, 11772

Other trials in United States

About this study

Official title: A Multi-Center, Open-Label Biomarker Study to Evaluate MN-166 in Subjects With Amyotrophic Literal Sclerosis (ALS)

This is a multi-center, open-label study of MN-166 (ibudilast) in subjects with ALS. To be eligible subjects must meet the El Escorial criteria of possible, laboratory-supported probable, probable, or definite criteria for a diagnosis of ALS. Safety, tolerability, blood, neuro-imaging biomarkers, and clinical outcomes will be collected on all subjects. Subjects will receive study drug for 36 weeks.

The study will consist of a Screening Phase (up to 6 weeks), an Open-Label Treatment Phase (36 weeks) and an Off-Treatment Follow-up Phase (4 Weeks).

Number of Subjects (Planned):

Approximately 45 subjects are planned to be screened with the goal of enrolling 35 subjects.

Read the detailed description

This is a multi-center, open-label study of MN-166 (ibudilast) in subjects with ALS. To be eligible subjects must meet the El Escorial criteria of possible, laboratory-supported probable, probable, or definite criteria for a diagnosis of ALS. Safety, tolerability, blood, neuro-imaging biomarkers, and clinical outcomes will be collected on all subjects. Subjects will receive study drug for 36 weeks.

The study will consist of a Screening Phase (up to 6 weeks), an Open-Label Treatment Phase (36 weeks) and a Off-Treatment Follow-up Phase (4 Weeks).

During the Screening Phase, eligible ALS subjects will sign an informed consent form and the following screening assessments will be performed: review of inclusion/exclusion criteria: El Escorial ALS Diagnostic criteria, medical history and demographics, ALS diagnosis history, physical and neurological examination, U. Penn upper motor Neuron Burden (UMNB), pulmonary function tests, vital signs including height and weight, blood for safety labs including TSPO affinity test, ECG and review and documentation of concomitant medications and therapies.

Screening Phase (up to 6 weeks) The Treatment Phase will consist of a Baseline visit and 3 subsequent clinic visits at Weeks 4, 12, 24, and 36. Telephone follow-ups will occur at Weeks 1, 2, 8, 16, 20, 28, and 32.

Open-Label Treatment Phase (36 weeks) At the Baseline visit, subjects will return to the clinic and the following assessments will be performed/administered: review of inclusion and exclusion criteria for continued eligibility, vital signs, blood for safety labs and biomarkers, ECG, ALSFRS-R questionnaire, slow vital capacity (SVC), baseline strength as measured by hand held dynamometry (HHD), and Columbia Suicide Severity Rating Scale (C-SSRS). At this visit, study drug will be dispensed, and adverse events, concomitant medications and therapies will be assessed and documented. At subsequent visits during the Treatment Phase, similar assessments will be performed.

In addition, a [11C]PBR28-PET scan will be performed once between the Screening and Baseline visit, and once between the Week 12 and Week 28 phone calls. The ALSFRS-R, SVC and U Penn Upper Motor Neuron Burden will be repeated on the same day as the PET scans.

The follow-up visit will consist of a telephone call to document adverse events and concomitant therapies

Being tested
ibudilast
Keywords
ALS
Medical subject headings
Amyotrophic Lateral Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ibudilastDrug

    Also called MN-166

    Ibudilast is a small molecule that crosses the blood-brain barrier after oral administration. Its potential as a neuroprotective agent is based on in vitro and in vivo evidence of its ability to reduce microglial activation, inhibit microglia-monocyte recruitment to the central nervous system (CNS), and trigger the release of neurotrophic factors.

  • IbudilastDrug

    Also called MN-166

    Ibudilast is a small molecule that crosses the blood-brain barrier after oral administration. Its potential as a neuroprotective agent is based on in vitro and in vivo evidence of its ability to reduce microglial activation, inhibit microglia-monocyte recruitment to the central nervous system (CNS), and trigger the release of neurotrophic factors.

Study groups in NCT02714036
Study groupRoleWhat they receive
RegularExperimentalParticipants will receive up to 100 mg /day MN-166 for 36 weeks. MN-166 dosing may vary based on individual tolerability.
Receives: Drug: ibudilast
FlexibleExperimentalParticipants will receive up to 100 mg /day MN-166 for 36 weeks. MN-166 dosing may vary based on individual tolerability. Participants will have all assessments except PET scans.
Receives: Drug: Ibudilast

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Impact of MN-166 on [11C]-PBR28 Uptake in the Motor Cortices and Brain Stem Measured by Positron Emission Tomography (PET) Imaging at 12 - 24 Weeks

    Glial activation will be estimated in eligible participants in the Regular arm by combined magnetic resonance positron emission tomography (MR-PET) using the [11C]-PBR28 radioligand. [11C]-PBR28 uptake is quantified as the ratio of the standardized uptake value (SUVR). An independent neuroimaging rater blinded to the clinical data will assess for quality control of the PBR28-PET images and SUVR. The primary analysis will be performed on the modified Intent-to-Treat (mITT) population. The median (90% confidence interval [CI]) changes from baseline in SUVR from pre- to post-treatment visit will be presented.

    Measured: 12- 24 weeks (post treatment [11C]-PBR28-PET scan will be performed between the Week 12 and Week 24 visits.

  2. Impact of MN-166 on Several Markers of Neuro-inflammation Measured by Blood Biomarkers at Week 36

    Mean change from baseline (pre-dose) to Week 36 in blood biomarkers for neuroinflammation, including macrophage migration inhibitory factor (MIF), tumor necrosis factor (TNF)-alpha, and neurofilament light (NfL). All blood biomarkers are measured in picograms/milliliter (pg/mL).

    Measured: 36 weeks

Secondary outcomes (4)

  1. Safety and Tolerability of MN-166 Over 36 Weeks

    Clinical and laboratory treatment-emergent adverse events (TEAEs) will be collected and stratified by severity, persistence over time, and relationship to study drug.

    Measured: 36 weeks

  2. Evaluate the Effect of MN-166 on ALS Clinical Outcomes (ALS Functional Rating Scale-revised [ALSFRS-R]) Over 36 Weeks.

    Mean change from baseline to Week 36 on ALSFRS-R score. ALSFRS-R rating scale is a tool to assess patient's capability and independence in 12 functional activities. The ALSFRS-R total score is a composite of sub-scores measuring speech, salivation, swallowing, handwriting, cutting food and handling utensils, dressing and hygiene, turning in bed and adjusting bed clothes, walking, climbing stairs, dyspnea, orthopnea, and respiratory insufficiency. Each subscale ranges from 0 (no ability) to 4 (normal ability). The ALSFRS-R score is the sum total ranging from 0 (zero) to 48, with higher scores meaning better outcome.

    Measured: 36 weeks

  3. Mean Change From Baseline in Slow Vital Capacity (Percent Predicted) Normal Volume at Week 36

    Slow vital capacity (SVC) is the maximum volume of air that can be slowly exhaled after slow, maximal inhalation, measured in liters. The maximum volume expired is converted to percent of predicted (% pred.) normal volume. Higher SVC (% pred.) normal volume indicates better pulmonary function. The results below reflect the mean change in SVC (% pred.) from baseline to week 36.

    Measured: 36 weeks

  4. Mean Change From Baseline in Isometric Strength as Measured by Hand-held Dynamometry (HHD) at Week 36.

    HHD assesses isometric strength using a MicroFET2 hand-held dynamometer in kilograms (kg). To calculate megascores, the mean and standard deviation of each muscle group, without regard to laterality, is calculated from the baseline assessment. Nine upper and lower extremity muscles or muscle groups were examined: shoulder flexion, elbow flexion, wrist extension, first dorsal interosseous contraction, hip flexion, knee extension, and ankle dorsiflexion. Each group was measured at least twice bilaterally and the average of the 2 highest measurements were analyzed. To calculate megascores, the mean and standard deviation of each group were calculated from baseline.

    Measured: 36 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Mar 2016 (estimated)
  2. Study start6 May 2016
  3. Primary completion31 Dec 2019
  4. Study completion30 Jun 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
35 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02714036
Sponsor's protocol ID
MN-166-ALS-1202
Status last verified
Sep 2024
First submitted
9 Mar 2016
Last updated
24 Sep 2024
Data monitoring committee
No
Individual data sharing
No

Publications

  • Al-Chalabi A, Hardiman O. The epidemiology of ALS: a conspiracy of genes, environment and time. Nat Rev Neurol. 2013 Nov;9(11):617-28. doi: 10.1038/nrneurol.2013.203. Epub 2013 Oct 15.

    PubMed 24126629

  • Chio A, Logroscino G, Hardiman O, Swingler R, Mitchell D, Beghi E, Traynor BG; Eurals Consortium. Prognostic factors in ALS: A critical review. Amyotroph Lateral Scler. 2009 Oct-Dec;10(5-6):310-23. doi: 10.3109/17482960802566824.

    PubMed 19922118

  • Chio A, Logroscino G, Traynor BJ, Collins J, Simeone JC, Goldstein LA, White LA. Global epidemiology of amyotrophic lateral sclerosis: a systematic review of the published literature. Neuroepidemiology. 2013;41(2):118-30. doi: 10.1159/000351153. Epub 2013 Jul 11.

    PubMed 23860588

  • Turner MR, Hardiman O, Benatar M, Brooks BR, Chio A, de Carvalho M, Ince PG, Lin C, Miller RG, Mitsumoto H, Nicholson G, Ravits J, Shaw PJ, Swash M, Talbot K, Traynor BJ, Van den Berg LH, Veldink JH, Vucic S, Kiernan MC. Controversies and priorities in amyotrophic lateral sclerosis. Lancet Neurol. 2013 Mar;12(3):310-22. doi: 10.1016/S1474-4422(13)70036-X.

    PubMed 23415570

  • Miller RG, Mitchell JD, Moore DH. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev. 2012 Mar 14;2012(3):CD001447. doi: 10.1002/14651858.CD001447.pub3.

    PubMed 22419278

  • Henkel JS, Beers DR, Siklos L, Appel SH. The chemokine MCP-1 and the dendritic and myeloid cells it attracts are increased in the mSOD1 mouse model of ALS. Mol Cell Neurosci. 2006 Mar;31(3):427-37. doi: 10.1016/j.mcn.2005.10.016. Epub 2005 Dec 5.

    PubMed 16337133

  • Boillee S, Yamanaka K, Lobsiger CS, Copeland NG, Jenkins NA, Kassiotis G, Kollias G, Cleveland DW. Onset and progression in inherited ALS determined by motor neurons and microglia. Science. 2006 Jun 2;312(5778):1389-92. doi: 10.1126/science.1123511.

    PubMed 16741123

  • Butovsky O, Siddiqui S, Gabriely G, Lanser AJ, Dake B, Murugaiyan G, Doykan CE, Wu PM, Gali RR, Iyer LK, Lawson R, Berry J, Krichevsky AM, Cudkowicz ME, Weiner HL. Modulating inflammatory monocytes with a unique microRNA gene signature ameliorates murine ALS. J Clin Invest. 2012 Sep;122(9):3063-87. doi: 10.1172/JCI62636. Epub 2012 Aug 6.

    PubMed 22863620

  • Koval ED, Shaner C, Zhang P, du Maine X, Fischer K, Tay J, Chau BN, Wu GF, Miller TM. Method for widespread microRNA-155 inhibition prolongs survival in ALS-model mice. Hum Mol Genet. 2013 Oct 15;22(20):4127-35. doi: 10.1093/hmg/ddt261. Epub 2013 Jun 4.

    PubMed 23740943

  • Brettschneider J, Del Tredici K, Toledo JB, Robinson JL, Irwin DJ, Grossman M, Suh E, Van Deerlin VM, Wood EM, Baek Y, Kwong L, Lee EB, Elman L, McCluskey L, Fang L, Feldengut S, Ludolph AC, Lee VM, Braak H, Trojanowski JQ. Stages of pTDP-43 pathology in amyotrophic lateral sclerosis. Ann Neurol. 2013 Jul;74(1):20-38. doi: 10.1002/ana.23937. Epub 2013 Jun 19.

    PubMed 23686809

  • Henkel JS, Engelhardt JI, Siklos L, Simpson EP, Kim SH, Pan T, Goodman JC, Siddique T, Beers DR, Appel SH. Presence of dendritic cells, MCP-1, and activated microglia/macrophages in amyotrophic lateral sclerosis spinal cord tissue. Ann Neurol. 2004 Feb;55(2):221-35. doi: 10.1002/ana.10805.

    PubMed 14755726

  • Kuhle J, Lindberg RL, Regeniter A, Mehling M, Steck AJ, Kappos L, Czaplinski A. Increased levels of inflammatory chemokines in amyotrophic lateral sclerosis. Eur J Neurol. 2009 Jun;16(6):771-4. doi: 10.1111/j.1468-1331.2009.02560.x. Epub 2009 Feb 19.

    PubMed 19236470

  • Moreau C, Devos D, Brunaud-Danel V, Defebvre L, Perez T, Destee A, Tonnel AB, Lassalle P, Just N. Elevated IL-6 and TNF-alpha levels in patients with ALS: inflammation or hypoxia? Neurology. 2005 Dec 27;65(12):1958-60. doi: 10.1212/01.wnl.0000188907.97339.76.

    PubMed 16380619

  • Zurcher NR, Loggia ML, Lawson R, Chonde DB, Izquierdo-Garcia D, Yasek JE, Akeju O, Catana C, Rosen BR, Cudkowicz ME, Hooker JM, Atassi N. Increased in vivo glial activation in patients with amyotrophic lateral sclerosis: assessed with [(11)C]-PBR28. Neuroimage Clin. 2015 Jan 19;7:409-14. doi: 10.1016/j.nicl.2015.01.009. eCollection 2015.

    PubMed 25685708

  • Sanftner LM, Gibbons JA, Gross MI, Suzuki BM, Gaeta FC, Johnson KW. Cross-species comparisons of the pharmacokinetics of ibudilast. Xenobiotica. 2009 Dec;39(12):964-77. doi: 10.3109/00498250903254340.

    PubMed 19925385

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing ibudilast in people with Amyotrophic Lateral Sclerosis, run by MediciNova at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Impact of MN-166 on [11C]-PBR28 Uptake in the Motor Cortices and Brain Stem Measured by Positron Emission Tomography (PET) Imaging at 12 - 24 Weeks (time frame: 12- 24 weeks (post treatment [11C]-PBR28-PET scan will be performed between the Week 12 and Week 24 visits.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02714036, which also lists 33 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2024.

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