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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Carolinas Healthcare System
Information provided by (Responsible Party):
MediciNova
ClinicalTrials.gov Identifier:
NCT02238626
First received: September 4, 2014
Last updated: August 10, 2017
Last verified: August 2017
  Purpose

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.


Condition Intervention Phase
Amyotrophic Lateral Sclerosis Drug: Placebo (for MN-166) Drug: MN-166 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Single-center, Randomized, Double-blind, Placebo-controlled, 6 Month Clinical Trial Followed by an Open-label Extension to Evaluate the Safety, Tolerability and Clinical Endpoint Responsiveness of Ibudilast (MN-166) in Subjects With Amyotrophic Lateral Sclerosis (ALS)

Resource links provided by NLM:


Further study details as provided by MediciNova:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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)


Other Outcome Measures:
  • 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


Estimated Enrollment: 120
Study Start Date: September 2014
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo (for MN-166)
Sugar pill manufactured for MN-166 10 mg tablets
Drug: Placebo (for MN-166)
Other Name: Sugar pill manufactured to mimic MN-166 10 mg tablet
Experimental: MN-166
MN-166 10 mg tablets (up to 60 mg/day) by mouth 2-3 times a day for 6 months
Drug: MN-166

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02238626

Locations
United States, North Carolina
Carolinas Healthcare System, Dept. of Neurology
Charlotte, North Carolina, United States, 28232-2861
Sponsors and Collaborators
MediciNova
Carolinas Healthcare System
Investigators
Principal Investigator: Benjamin R Brooks, M.D. Carolinas Healthcare System
  More Information

Additional Information:
Responsible Party: MediciNova
ClinicalTrials.gov Identifier: NCT02238626     History of Changes
Other Study ID Numbers: MN-166-ALS-1201
Study First Received: September 4, 2014
Last Updated: August 10, 2017

Keywords provided by MediciNova:
amyotrophic lateral sclerosis
pharmacotherapy
intervention
prospective
safety endpoint
preliminary efficacy
ibudilast

Additional relevant MeSH terms:
Sclerosis
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Ibudilast
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Vasodilator Agents

ClinicalTrials.gov processed this record on August 21, 2017