Amyotrophic Lateral SclerosisPhase 2IBU-ALS-1201NCT02238626
Ibudilast (MN-166) in Subjects With Amyotrophic Lateral Sclerosis (ALS)
A Phase 2 study testing MN-166 and riluzole in people with Amyotrophic Lateral Sclerosis, run by MediciNova at 1 site in United States.
Trial summary
This is a single center, randomized, double-blind, placebo-controlled, 6-month study designed to evaluate the safety, tolerability and clinical responsiveness of MN-166/ibudilast (60 mg/day) when administered as an adjunct to riluzole (100 mg/day) in 60 subjects with ALS. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- MN-166 and riluzole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2014to Dec 2017
- Phase
- Phase 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent is obtained and willing and able to comply with the protocol in the opinion of the Investigator.
- Male or female subjects ages ≥ 18 to 80 years, inclusive
- Diagnosis of familial or sporadic ALS as defined by the El Escorial-Revised (2000) research diagnostic criteria for ALS [Clinically Definite, Clinically Probable, Probable-Laboratory-Supported]
- Diagnosis of ALS with onset of less than or equal to 5 years from first clinical weakness
- Slow vital capacity ≥ 60% of predicted within 1 month prior to Treatment Day 1
- Currently on a stable dose of riluzole for at least 30 days prior to initiation of study drug. Subjects not currently taking riluzole will be started on 50 mg qd for the first 7 days followed by 50 mg bid for the following 21 days prior to screening. Patients may be screened during this time period but not started on study drug until they are on a stable dose of riluzole.
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- All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing). Females of childbearing potential must use an effective method of contraception throughout the entire study period and for 30 days after study drug discontinuation.
- Females must not be lactating or pregnant at Screening or Baseline (as documented by a negative beta-human chorionic gonadotropin [ß-hCG] (or human chorionic gonadotropin [hCG]). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
- Males should practice contraception as follows: condom use and contraception by female partner.
- Able to swallow study medication capsules.
- Subject is willing and able to comply with the protocol assessments and visits, in the opinion of the study nurse/coordinator and the Investigator.
- Has no known allergies to the study drug or its excipients.
- Has received 23-valent pneumococcal vaccine within 4 years prior to starting clinical trial.
- Diagnosis of ALS with onset of ≤10 years from first clinical weakness
- On Non-invasive ventilator with Non-invasive pressure [P-NIV] or volume [V-NIV] cycled ventilation stable use for ≥ 4 hours daily for 1 month prior to Treatment Day.
- Slow vital capacity ≥ 20% of predicted (Knudsen 1983) within 1 month prior to Treatment Day 1
- Able to swallow study medication capsules or have gastrostomy tube access for delivery of contents of medication capsule.
Who cannot join
- Use of tracheostomy, tracheostomy invasive mechanical ventilation [TIMV].
- Greater than 3% predicted loss in post-diagnosis vital capacity per month or a greater than 1 unit loss in post diagnosis ALSFRS-R total score per month [ exclusive of loss due to beginning use of assistive devices]
- Confirmed hepatic insufficiency or abnormal liver function (AST and/or ALT greater than 3 times the upper limit of the normal range)
- Renal insufficiency as defined by a serum creatinine greater than 1.5 times the upper limit of normal range
- Currently has a clinically significant psychiatric disorder or dementia which would preclude evaluation of symptoms.
- Has a clinically significant medical condition (other than ALS) including the following: neurological, metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, urological disorder, or central nervous system infection that would pose a risk to the subject if they were to participate in the study or that might confound the results of the study.
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- History of malignancy < 5 years prior to signing the informed consent, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
- ECG finding of QTcB prolongation > 450 ms for males and > 470 ms for females at screening
- History of HIV (human immunodeficiency virus), clinically significant chronic hepatitis, or other active infection
- Subject has a history of stomach or intestinal surgery or any other condition that could interfere with or is judged by the Investigator to interfere with absorption, distribution, metabolism, or excretion of study drug.
- Subject has a history of alcohol or substance abuse (DSM-IV-TR criteria) within 3 months prior to screening or alcohol or substance dependence (DSM-IV-TR criteria) within 12 months prior to screening.
- Subject has poor peripheral venous access that will limit the ability to draw blood as judged by the Investigator.
- Currently participating, or has participated in, a study with an investigational or marketed compound or device within 3 months prior to signing the informed consent.
- Unable to cooperate with any study procedures, unlikely to adhere to the study procedures and keep appointments, in the opinion of the Investigator.
- Advanced ALS group will follow the same inclusion/exclusion as the early ALS subjects with the exception of the following:
- Use of tracheostomy, tracheostomy invasive mechanical ventilation [TIMV].
- No rate of progression exclusion.
Trial locations and contacts
1 site in 1 country.
United States1 site
Carolinas Healthcare System, Dept. of Neurology
Charlotte, North Carolina, 28232-2861
About this study
Official title: A Single-center, Randomized, Double-blind, Placebo-controlled, 6-month Trial Followed by an Open-label Extension to Evaluate the Safety, Tolerability and Clinical Endpoint Responsiveness of Ibudilast (MN-166) in Subjects With (ALS)
This is a single center, randomized, double-blind, placebo-controlled, 6-month study designed to evaluate the safety, tolerability and clinical responsiveness of MN-166/ibudilast (60 mg/day) when administered as an adjunct to riluzole (100 mg/day) in 60 subjects with ALS.
This study will consist of two treatment arms, MN-166 and matching placebo. Randomization will occur in a 2:1 ratio (MN- 166: placebo).
Read more
Duration of Treatment: Screening Phase: up to 3 months; Double-blind Phase: 6 months; Open-label Phase 6 months (for placebo subjects only); Follow-up Phase: 2 weeks after last dose.
During treatment phase, subjects return to the clinic at Months 3 and 6 and will be telephoned by staff at Months 1,2,4, and 5 to collect information about side effects and new or concomitant medications.
All subjects (subjects who complete the Double-blind Phase and subjects who complete the Open-label Phase) or prematurely discontinue will return for a follow-up visit approximately 2 weeks after the last dose of study drug to assess adverse event status and to document concomitant medications.
Safety will be assessed by monitoring and recording all treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs) and discontinuations due to TEAEs. Additional assessments will include regular monitoring of hematology, blood chemistry, and urine values, regular measurement of vital signs, ECGs, medical history, physical and neurological examinations.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- Placebo (for MN-166), MN-166, riluzole
- Keywords
- amyotrophic lateral sclerosis, pharmacotherapy, intervention, prospective, safety endpoint, preliminary efficacy, ibudilast
- 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.
Placebo (for MN-166)Drug
Also called Sugar pill manufactured to mimic MN-166 10 mg tablet
MN-166Drug
Also called ibudilast
riluzoleDrug
Also called Rilutek
Patient is given 50 mg riluzole twice daily.
| Study group | Role | What they receive |
|---|---|---|
| Placebo (for MN-166) | Placebo comparator | Sugar pill manufactured for MN-166 10 mg tablets plus 50 mg riluzole by mouth twice daily for 6 months. Receives: Drug: Placebo (for MN-166); Drug: riluzole |
| MN-166 | Experimental | MN-166 10 mg tablets (up to 60 mg/day) by mouth 2-3 times a day plus 50 mg riluzole 2 times a day by mouth for 6 months. Receives: Drug: MN-166; Drug: riluzole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability of MN-166 60 mg/d Versus Placebo When Administered With Riluzole in Subjects With ALS
Safety will be assessed by monitoring and recording all treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs) and discontinuations due to TEAEs and Additional assessments will include regular monitoring of hematology, blood chemistry, and urine values, regular measurement of vital signs, ECGs, medical history, physical and neurological examinations.
Measured: 6 months
Secondary outcomes (6)
Mean Change in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised Total Score From Baseline to Month 6
Functional activity as assessed by the Amyotrophic Lateral Sclerosis Functional Rating Scale-revised from baseline visit to Month 6. The best possible score is 48; the worst possible score is 0. Typically, ALS scores decline. In this outcome, the change in score will be a negative value, e.g., -4, -8, etc. The higher negative value indicates greater decline in functional activity (change in score -8 is worse than change in score -4).
Measured: 6 months
Respiratory Function
Change in respiratory function (breathing capacity) from baseline to Month 6, as measured by slow vital capacity, in which the patient breathes into a spirometer slowly until the lungs are cleared of air. SVC is measured in liters (L). The greater the mean change from baseline to 6 months, the worse the outcome. For example, -10 is worse than -6.
Measured: 6 months
Muscle Strength
Muscle strength measured by manual muscle testing (MMT) and instrumented hand-held dynamometry. Maximum muscle strength is assessed by measuring the best of 2 handgrips represented as kilograms (kg). The greater the change from baseline to month 6, the worse off the subject is. For example, a change of -0.50 is worse than -0.40.
Measured: 6 months
Use of Non-invasive Ventilation
Non-invasive ventilation (NIV) utilization measured by clinically indicated prescription for NIV intervention and time to clinically indicated prescription for NIV intervention in each group (for early ALS subjects only). This is intended to count the number of subjects who had to go on non-invasive ventilation, as prescribed by the Principal Investigator, during study participation.
Measured: 6 months
The Mean Change in Baseline to Month 6 in Quality of Life as Measured by the Amyotrophic Lateral Sclerosis Assessment Questionnaire - 5
A patient self-reported questionnaire specifically designed to measure 5 areas of health: physical mobility, activities of daily living and independence, eating and drinking, communication, and emotional functioning. The ALSAQ-5 is brief and easy to complete questionnaire and has undergone rigorous testing for validity, reliability, and sensitivity to change and has been shown to be a robust tool for assessing ALS. The lowest possible score is 0 and the highest possible score is 20. The greater the mean decrease from baseline to Month 6, the group was considered worse off. For example, -2 is worse than -1. The greater the mean increase from baseline to Month 6, the group was considered improved. For example, 2 is better than 1.
Measured: 6 months
Clinical Global Impression of Change (CGIC)
A scale used to provide a global rating of illness severity, improvement, and response to treatment. It is a 3-item observer rating scale and uses a 7-point rating scale. The scale was rated relative to the previous standard of care visit prior to randomization for entry, i.e., -3 much much much worse, -2 much much worse, - 1 much worse, 0 no change, +1 much better, +2 much much better, +3 much, much, much better. Ratings were provided by the Investigator. The greater the mean decrease from baseline to Month 6, the group was considered worse off. For example, -2 is worse than -1. The greater the mean increase from baseline to Month 6, the group was considered improved. For example, 2 is better than 1.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2014 (estimated)
- Study startSep 2014
- Primary completionAug 2017
- Study completionDec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- MediciNova
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Wake Forest University Health Sciences
- Responsible party
- Sponsor
- Investigators
- Benjamin R Brooks, M.D., Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02238626
- Sponsor's protocol ID
- MN-166-ALS-1201
- Acronym
- IBU-ALS-1201
- Status last verified
- Oct 2021
- First submitted
- 4 Sep 2014
- Last updated
- 5 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-center, Randomized, Double-blind, Placebo-controlled, 6-month Trial Followed by an Open-label Extension to Evaluate the Safety, Tolerability and Clinical Endpoint Responsiveness of Ibudilast (MN-166) in Subjects With (ALS)
- ClinicalTrials.gov ID
- NCT02238626
- Acronym / sponsor ID
- IBU-ALS-1201 / MN-166-ALS-1201
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- amyotrophic lateral sclerosis, pharmacotherapy, intervention, prospective, safety endpoint, preliminary efficacy, ibudilast
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- MediciNovaIndustry (pharma, biotech, devices)
- Collaborators
- Wake Forest University Health Sciences
- Study start
- Sep 2014 (actual)
- Primary completion
- Aug 2017 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 12 Sep 2014 (estimated)
- Results
- Posted 5 Nov 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single center, randomized, double-blind, placebo-controlled, 6-month study designed to evaluate the safety, tolerability and clinical responsiveness of MN-166/ibudilast (60 mg/day) when administered as an adjunct to riluzole (100 mg/day) in 60 subjects with ALS.
This study will consist of two treatment arms, MN-166 and matching placebo. Randomization will occur in a 2:1 ratio (MN- 166: placebo).
Duration of Treatment: Screening Phase: up to 3 months; Double-blind Phase: 6 months; Open-label Phase 6 months (for placebo subjects only); Follow-up Phase: 2 weeks after last dose.
During treatment phase, subjects return to the clinic at Months 3 and 6 and will be telephoned by staff at Months 1,2,4, and 5 to collect information about side effects and new or concomitant medications.
All subjects (subjects who complete the Double-blind Phase and subjects who complete the Open-label Phase) or prematurely discontinue will return for a follow-up visit approximately 2 weeks after the last dose of study drug to assess adverse event status and to document concomitant medications.
Safety will be assessed by monitoring and recording all treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs) and discontinuations due to TEAEs. Additional assessments will include regular monitoring of hematology, blood chemistry, and urine values, regular measurement of vital signs, ECGs, medical history, physical and neurological examinations.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo (for MN-166) | Placebo comparator | Drug: Placebo (for MN-166), Drug: riluzoleSugar pill manufactured for MN-166 10 mg tablets plus 50 mg riluzole by mouth twice daily for 6 months. |
| MN-166 | Experimental | Drug: MN-166, Drug: riluzoleMN-166 10 mg tablets (up to 60 mg/day) by mouth 2-3 times a day plus 50 mg riluzole 2 times a day by mouth for 6 months. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Written informed consent is obtained and willing and able to comply with the protocol in the opinion of the Investigator.
- Male or female subjects ages ≥ 18 to 80 years, inclusive
- Diagnosis of familial or sporadic ALS as defined by the El Escorial-Revised (2000) research diagnostic criteria for ALS [Clinically Definite, Clinically Probable, Probable-Laboratory-Supported]
- Diagnosis of ALS with onset of less than or equal to 5 years from first clinical weakness
- Slow vital capacity ≥ 60% of predicted within 1 month prior to Treatment Day 1
Key exclusion criteria (17 listed)
- Use of tracheostomy, tracheostomy invasive mechanical ventilation [TIMV].
- Greater than 3% predicted loss in post-diagnosis vital capacity per month or a greater than 1 unit loss in post diagnosis ALSFRS-R total score per month [ exclusive of loss due to beginning use of assistive devices]
- Confirmed hepatic insufficiency or abnormal liver function (AST and/or ALT greater than 3 times the upper limit of the normal range)
- Renal insufficiency as defined by a serum creatinine greater than 1.5 times the upper limit of normal range
- Currently has a clinically significant psychiatric disorder or dementia which would preclude evaluation of symptoms.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo (for MN-166)Also: Sugar pill manufactured to mimic MN-166 10 mg tablet | Drug | Placebo (for MN-166) |
| MN-166Also: ibudilast | Drug | MN-166 |
| riluzoleAlso: RilutekPatient is given 50 mg riluzole twice daily. | Drug | MN-166, Placebo (for MN-166) |
Primary outcome
Safety and Tolerability of MN-166 60 mg/d Versus Placebo When Administered With Riluzole in Subjects With ALS
Time frame: 6 months
Safety will be assessed by monitoring and recording all treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs) and discontinuations due to TEAEs and Additional assessments will include regular monitoring of hematology, blood chemistry, and urine values, regular measurement of vital signs, ECGs, medical history, physical and neurological examinations.
6 secondary outcomes
Mean Change in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised Total Score From Baseline to Month 6
Time frame: 6 months
Respiratory Function
Time frame: 6 months
Muscle Strength
Time frame: 6 months
Use of Non-invasive Ventilation
Time frame: 6 months
The Mean Change in Baseline to Month 6 in Quality of Life as Measured by the Amyotrophic Lateral Sclerosis Assessment Questionnaire - 5
Time frame: 6 months
Clinical Global Impression of Change (CGIC)
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Please call 1-844-CMC-ALS1 (1-844-262-2571) toll free for information on this trial.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Benjamin R Brooks, M.D. principal investigator
Wake Forest University Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MN-166 and riluzole in people with Amyotrophic Lateral Sclerosis, run by MediciNova at 1 site 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 17 inclusion and 17 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 5 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
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 5 Nov 2021). 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?
Safety and Tolerability of MN-166 60 mg/d Versus Placebo When Administered With Riluzole in Subjects With ALS (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Nov 2021.