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

NCT02714036 | Completed Phase 1 Results

• 1 other identifier: MN-166-ALS-1202
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

ALS

Outcome Measures

Primary Outcomes (2)

• 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.

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

• 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).

  36 weeks

Secondary Outcomes (4)

• Safety and Tolerability of MN-166 Over 36 Weeks

  36 weeks

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

  36 weeks

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

  36 weeks

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

  36 weeks

Study Arms (2)

Regular

EXPERIMENTAL

Participants will receive up to 100 mg /day MN-166 for 36 weeks. MN-166 dosing may vary based on individual tolerability.

Drug: ibudilast

Flexible

EXPERIMENTAL

Participants 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.

Drug: Ibudilast

Interventions

Ibudilast DRUG

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.

Also known as: MN-166

Regular

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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)

You may not qualify if:

• 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)
• 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)

Sponsors & Collaborators

• MediciNova: lead
• Massachusetts General Hospital: collaborator
• South Shore Neurologic Associates: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

South Shore Neurologic Associates, P.C.

Patchogue, New York, 11772, United States

Location

Related Publications (33)

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MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

ibudilast

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Director, Research and Development
• Organization: MEDICINOVA, INC

clinicaltrialinfo@medicinova.com

858-373-1500

Study Officials

• Suma Babu, MBBS, MPH

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Participants were assigned to one of 2 groups at the discretion of the Principal Investigator.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2016
• First Posted: March 21, 2016
• Study Start: May 6, 2016
• Primary Completion: December 31, 2019
• Study Completion: June 30, 2020
• Last Updated: September 24, 2024
• Results First Posted: September 24, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)