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Ibudilast (MN-166) in Subjects With Amyotrophic Lateral Sclerosis (ALS) (IBU-ALS-1201)

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ClinicalTrials.gov Identifier: NCT02238626
Recruitment Status : Completed
First Posted : September 12, 2014
Last Update Posted : February 15, 2021
Sponsor:
Collaborator:
Atrium Health
Information provided by (Responsible Party):
MediciNova

Tracking Information
First Submitted Date  ICMJE September 4, 2014
First Posted Date  ICMJE September 12, 2014
Last Update Posted Date February 15, 2021
Actual Study Start Date  ICMJE September 2014
Actual Primary Completion Date August 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 10, 2014)
Evaluate 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 23, 2015)
  • The secondary objective is to evaluate the clinical endpoint responsiveness of MN-166 60 mg/d versus placebo when administered with riluzole in subjects with amyotrophic lateral sclerosis as measured by Functional Activity [ Time Frame: 6 months ]
    Functional activity as assessed by the Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-R)
  • The secondary objective is to evaluate the clinical endpoint responsiveness of MN-166 60 mg/d versus placebo when administered with riluzole in subjects with amyotrophic lateral sclerosis as measured by Respiratory Function [ Time Frame: 6 months ]
    Respiratory function as measured by slow vital capacity (SVC), Maximum Inspiratory Pressure (MIP) also known as Negative Inspiratory Force (NIF) and Forced Expiratory Volume in 1 second (FEV1) measured under SVC protocol and Maximal Voluntary Ventilation (MVV).
  • The secondary objective is to evaluate the clinical endpoint responsiveness of MN-166 60 mg/d versus placebo when administered with riluzole in subjects with amyotrophic lateral sclerosis as measured by Muscle Strength [ Time Frame: 6 months ]
    Muscle strength measured by manual muscle testing (MMT) and instrumented hand grip dynamometry
  • The secondary objective is to evaluate the clinical endpoint responsiveness of MN-166 60 mg/d versus placebo when administered with riluzole in subjects with amyotrophic lateral sclerosis as measured by Non-Invasion Ventilation (NIV) [ Time Frame: 6 months ]
    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)
Original Secondary Outcome Measures  ICMJE
 (submitted: September 10, 2014)
  • The secondary objective is to evaluate the clinical endpoint responsiveness of MN-166 60 mg/d versus placebo when administered with riluzole in subjects with amyotrophic lateral sclerosis as measured by Functional Activity [ Time Frame: 6 months ]
    Functional activity as assessed by the Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-R)
  • The secondary objective is to evaluate the clinical endpoint responsiveness of MN-166 60 mg/d versus placebo when administered with riluzole in subjects with amyotrophic lateral sclerosis as measured by Respiratory Function [ Time Frame: 6 months ]
    Respiratory function as measured by slow vital capacity (SVC), Maximum Inspiratory Pressure (MIP) also known as Negative Inspiratory Force (NIF) and Forced Expiratory Volume in 1 second (FEV1) measured under SVC protocol
  • The secondary objective is to evaluate the clinical endpoint responsiveness of MN-166 60 mg/d versus placebo when administered with riluzole in subjects with amyotrophic lateral sclerosis as measured by Muscle Strength [ Time Frame: 6 months ]
    Muscle strength measured by manual muscle testing (MMT) and instrumented hand grip dynamometry
  • The secondary objective is to evaluate the clinical endpoint responsiveness of MN-166 60 mg/d versus placebo when administered with riluzole in subjects with amyotrophic lateral sclerosis as measured by Non-Invasion Ventilation (NIV) [ Time Frame: 6 months ]
    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
Current Other Pre-specified Outcome Measures
 (submitted: September 10, 2014)
  • Evaluate quality of life [ Time Frame: 6 months ]
    To evaluate quality of life as assessed by the Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-5)
  • Evaluate Clinical Global Impression of Change (CGIC) [ Time Frame: 6 months ]
    To evaluate Clinical Global Impression of Change (CGIC) as assessed by ALS subjects, caregivers and physician anchored to most recent standard of care visit prior to screening visit
  • Evaluate Disease Progression [ Time Frame: 6 months ]
    To evaluate serum creatinine as a biomarker for disease progression
  • Cmax [ Time Frame: Month 6 ]
    To evaluate the Cmax of MN-166 when administered as an adjunct to riluzole.
  • Tmax [ Time Frame: Month 6 ]
    To evaluate the Tmax of MN-166 when administered as an adjunct to riluzole.
  • AUC [ Time Frame: Month 6 ]
    To evaluate the AUC of MN-166 when administered as an adjunct to riluzole.
  • T1/2 [ Time Frame: Month 6 ]
    To evaluate the half-life of MN-166 when administered as an adjunct to riluzole
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Ibudilast (MN-166) in Subjects With Amyotrophic Lateral Sclerosis (ALS)
Official Title  ICMJE 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)
Brief 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.

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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Amyotrophic Lateral Sclerosis
Intervention  ICMJE
  • Drug: Placebo (for MN-166)
    Other Name: Sugar pill manufactured to mimic MN-166 10 mg tablet
  • Drug: MN-166
    Other Name: ibudilast
  • Drug: riluzole
    Patient is given 50 mg riluzole twice daily.
    Other Name: Rilutek
Study Arms  ICMJE
  • Placebo Comparator: Placebo (for MN-166)
    Sugar pill manufactured for MN-166 10 mg tablets plus 50 mg riluzole by mouth twice daily for 6 months.
    Interventions:
    • Drug: Placebo (for MN-166)
    • Drug: riluzole
  • Experimental: 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.
    Interventions:
    • Drug: MN-166
    • Drug: riluzole
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 29, 2018)
71
Original Estimated Enrollment  ICMJE
 (submitted: September 10, 2014)
60
Actual Study Completion Date  ICMJE December 2017
Actual Primary Completion Date August 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.
  • 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.

Exclusion Criteria:

  • 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.
  • 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:

Inclusion criteria:

  • 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.

Exclusion criteria:

  • Use of tracheostomy, tracheostomy invasive mechanical ventilation [TIMV].
  • No rate of progression exclusion.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02238626
Other Study ID Numbers  ICMJE MN-166-ALS-1201
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party MediciNova
Study Sponsor  ICMJE MediciNova
Collaborators  ICMJE Atrium Health
Investigators  ICMJE
Principal Investigator: Benjamin R Brooks, M.D. Atrium Health
PRS Account MediciNova
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP