Phase 2
N=35
A Biomarker Study to Evaluate MN-166 in Subjects With Amyotrophic Literal Sclerosis (ALS)
Amyotrophic Lateral Sclerosis
Bottom Line
View on ClinicalTrials.gov: NCT02714036 ↗Enrolled (actual)
35
Serious AEs
17.1%
Results posted
Sep 2024
Primary outcome: Primary: 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 — 0.0015 SUV ratio
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- ibudilast (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- MediciNova
- Primary completion
- Dec 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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 |
0.0015 | — |
| PRIMARY Impact of MN-166 on Several Markers of Neuro-inflammation Measured by Blood Biomarkers at Week 36 |
-673387.22; -0.31; 21.43 | — |
| SECONDARY Safety and Tolerability of MN-166 Over 36 Weeks |
30; 5 | — |
| SECONDARY Evaluate the Effect of MN-166 on ALS Clinical Outcomes (ALS Functional Rating Scale-revised [ALSFRS-R]) Over 36 Weeks. |
-4.5 | — |
| SECONDARY Mean Change From Baseline in Slow Vital Capacity (Percent Predicted) Normal Volume at Week 36 |
-9.27 | — |
| SECONDARY Mean Change From Baseline in Isometric Strength as Measured by Hand-held Dynamometry (HHD) at Week 36. |
-0.5803; -0.5004; -0.5324; -0.2778; -0.3525; -0.3151 | — |
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.
Eligibility Criteria
Inclusion Criteria
- 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)
Exclusion Criteria
- 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)
- 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:
Data sourced from ClinicalTrials.gov (NCT02714036). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.