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| Name | Class |
|---|---|
| Wake Forest University Health Sciences | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo (for MN-166) | Drug |
|
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| 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). |
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Inclusion Criteria:
Exclusion Criteria:
Advanced ALS group will follow the same inclusion/exclusion as the early ALS subjects with the exception of the following:
Inclusion criteria:
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Benjamin R Brooks, M.D. | Wake Forest University Health Sciences | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Carolinas Healthcare System, Dept. of Neurology | Charlotte | North Carolina | 28232-2861 | United States |
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| Label | URL |
|---|---|
| Please call 1-844-CMC-ALS1 (1-844-262-2571) toll free for information on this trial. | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo (for MN-166) (Early ALS Cohort) | Sugar pill manufactured for MN-166 10 mg tablets plus 50 mg riluzole by mouth twice daily for 6 months. Placebo (for MN-166) riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS onset is 5 years or less. |
| FG001 | MN-166 (Early ALS Cohort) | 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. MN-166 riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS onset is 5 years or less. |
| FG002 | Placebo (Advanced ALS Cohort) | Sugar pill manufactured for MN-166 10 mg tablets plus 50 mg riluzole by mouth twice daily for 6 months. Placebo (for MN-166) riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS onset more than 5 years, but less than 10 years. |
| FG003 | MN-166 (Advanced ALS Cohort) | 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. MN-166 riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS onset is less than 10 years, but more than 5 years. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Early ALS Cohort: Patient ALS symptom onset 5 years or less before screening. Advanced ALS Cohort: Patient ALS symptom onset between 5 and 10 years before screening.
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo (for MN-166) (Early ALS Cohort) | Sugar pill manufactured for MN-166 10 mg tablets plus 50 mg riluzole by mouth twice daily for 6 months. Placebo (for MN-166) riluzole: Patient is given 50 mg riluzole twice daily. |
| BG001 | MN-166 (Early ALS Cohort) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Safety analysis population included all randomized subjects who received at least one dose of study drug and had at least one post-dose safety assessment. | Posted | Count of Participants | Participants | 6 months |
|
Adverse events were collected from Baseline to end of double-blind treatment (6 months).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo (for MN-166) (Early ALS Cohort) | Sugar pill manufactured for MN-166 10 mg tablets plus 50 mg riluzole by mouth twice daily for 6 months. Placebo (for MN-166) riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS onset within 5 years of screening. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| dysphagia | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| muscle weakness | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Director, Scientific Affairs | MediciNova, Inc. | 8583444535 | makhay@medicinova.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 31, 2016 | Jun 9, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000690 | Amyotrophic Lateral Sclerosis |
| ID | Term |
|---|---|
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D016472 | Motor Neuron Disease |
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| ID | Term |
|---|---|
| D000073893 | Sugars |
| D013607 | Tablets |
| C038366 | ibudilast |
| D019782 | Riluzole |
| ID | Term |
|---|---|
| D002241 | Carbohydrates |
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
| D013844 | Thiazoles |
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| MN-166 |
| Drug |
|
|
| riluzole | Drug | Patient is given 50 mg riluzole twice daily. |
|
|
| 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. | 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. | 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. | 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. | 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. | 6 months |
| Lost to Follow-up |
|
| Withdrawal by Subject |
|
| Death |
|
| Other |
|
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. MN-166 riluzole: Patient is given 50 mg riluzole twice daily. |
| BG002 | Placebo (for MN-166) (Advanced ALS Cohort) | Sugar pill manufactured for MN-166 10 mg tablets plus 50 mg riluzole by mouth twice daily for 6 months. Placebo (for MN-166) riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS symptom onset between 5 and 10 years of Screening. |
| BG003 | MN-166 (Advanced ALS Cohort) | 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. MN-166 riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS symptom onset between 5 and 10 years before screening. |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG001 | MN-166 | 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. MN-166 riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS onset within 5 years. |
| OG002 | Placebo (for MN-166) (Advanced ALS Cohort) | Sugar pill manufactured for MN-166 10 mg tablets plus 50 mg riluzole by mouth twice daily for 6 months. Placebo (for MN-166) riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS symptom onset between 5 and 10 years before Screening. |
| OG003 | MN-166 (Advanced ALS Cohort) | 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. MN-166 riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS symptom onset between 5 and 10 years before Screening. |
|
|
| Secondary | 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). | Safety Population | Posted | Mean | Standard Deviation | score on a scale | 6 months |
|
|
|
| Secondary | 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. | Subjects who completed Month 6 (double-blind treatment phase) | Posted | Mean | Standard Deviation | Liters | 6 months |
|
|
|
| Secondary | 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. | Subjects who completed Month 6 (double-blind treatment phase) | Posted | Mean | Standard Deviation | weight (kg) | 6 months |
|
|
|
| Secondary | 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. | Full Analysis Set | Posted | Count of Participants | Participants | No | 6 months |
|
|
|
| Secondary | 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. | Full analysis set | Posted | Mean | Standard Deviation | score on a scale | 6 months |
|
|
|
| Secondary | 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. | Full analysis set | Posted | Mean | Standard Deviation | score on a scale | 6 months |
|
|
|
| 0 |
| 17 |
| 1 |
| 17 |
| 17 |
| 17 |
| EG001 | MN-166 (Early ALS Cohort) | 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. MN-166 riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS onset within 5 years of screening. | 1 | 34 | 5 | 34 | 34 | 34 |
| EG002 | Placebo (for MN-166) (Advanced ALS Cohort) | Sugar pill manufactured for MN-166 10 mg tablets plus 50 mg riluzole by mouth twice daily for 6 months. Placebo (for MN-166) riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS symptom onset between 5 and 10 years of Screening. | 1 | 8 | 2 | 8 | 8 | 8 |
| EG003 | MN-166 (Advanced ALS Cohort) | 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. MN-166 riluzole: Patient is given 50 mg riluzole twice daily. Patient ALS symptom onset between 5 and 10 years before screening. | 1 | 11 | 3 | 11 | 11 | 11 |
| intestinal obstruction | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
|
| pneumonia | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
|
| pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
|
| Lower limb fracture | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
|
| Hydronephrosis | Renal and urinary disorders | MedDRA 21.0 | Systematic Assessment |
|
| Ureterolithiasis | Renal and urinary disorders | MedDRA 21.0 | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA 21.0 | Systematic Assessment |
|
| Ankle fracture | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
|
| amyotrophic lateral sclerosis | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
|
| aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 21.0 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 21.0 | Systematic Assessment |
|
| muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
|
| nausea | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
|
| weight decreased | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
|
| dyspnea | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
|
| injury | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
|
| headache | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
|
| mobility decreased | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
|
| dysphagia | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
|
| salivary hypersecretion | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
|
| skin abrasion | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
|
| respiratory distress | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
|
| abdominal distention | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
|
| diarrhea | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
|
| upper respiratory tract infection | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
|
| gastrostomy | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
|
| edema peripheral | Vascular disorders | MedDRA 21.0 | Systematic Assessment |
|
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| D019636 | Neurodegenerative Diseases |
| D057177 | TDP-43 Proteinopathies |
| D009468 | Neuromuscular Diseases |
| D057165 | Proteostasis Deficiencies |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D013457 |
| Sulfur Compounds |
| D009930 | Organic Chemicals |
| D052160 | Benzothiazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |