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    Summary
    EudraCT Number:2019-003549-14
    Sponsor's Protocol Code Number:MN-166-ALS-2301
    National Competent Authority:Hungary - National Institute of Pharmacy
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2020-01-13
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedHungary - National Institute of Pharmacy
    A.2EudraCT number2019-003549-14
    A.3Full title of the trial
    A PHASE 2B/3, MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 12 MONTH CLINICAL TRIAL TO EVALUATE THE EFFICACY AND SAFETY OF MN-166 (IBUDILAST) FOLLOWED BY AN OPEN-LABEL EXTENSION IN SUBJECTS WITH AMYOTROPHIC LATERAL SCLEROSIS
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Clinical Trial To Evaluate The Efficacy And Safety Of Mn-166 (Ibudilast) In Subjects With Amyotrophic Lateral Sclerosis(Lou Gehrig's disease)
    A.3.2Name or abbreviated title of the trial where available
    COMBAT-ALS
    A.4.1Sponsor's protocol code numberMN-166-ALS-2301
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorMediciNova, Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportMediciNova, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAccelsiors CRO and Consultancy Services Ltd
    B.5.2Functional name of contact pointRegulatory Unit
    B.5.3 Address:
    B.5.3.1Street Address103 Haros Str.
    B.5.3.2Town/ cityBudapest
    B.5.3.3Post code1222
    B.5.3.4CountryHungary
    B.5.4Telephone number+361299 00 91
    B.5.5Fax number+381-2167-42-999
    B.5.6E-mailregulatory@accelsiors.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/16/1801
    D.3 Description of the IMP
    D.3.1Product nameIbudilast
    D.3.2Product code MN-166
    D.3.4Pharmaceutical form Capsule
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNIBUDILAST
    D.3.9.1CAS number 50847-11-5
    D.3.9.2Current sponsor codeMN-166
    D.3.9.4EV Substance CodeSUB08096MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboCapsule
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Amyotrophic Lateral Sclerosis
    E.1.1.1Medical condition in easily understood language
    Amyotrophic Lateral Sclerosis a life-threatening disease that includes following symptoms:cramps, spasticity, muscle weakness, slurred or nasal speech, atrophy, weakness, fatigue, shortness of breath.
    E.1.1.2Therapeutic area Diseases [C] - Nervous System Diseases [C10]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10002026
    E.1.2Term Amyotrophic lateral sclerosis
    E.1.2System Organ Class 10029205 - Nervous system disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of the study is to evaluate the efficacy of MN-166 versus placebo on patient’s functional activity measured by ALSFRS-R score and time to survival in ALS subjects.
    E.2.2Secondary objectives of the trial
    The secondary objective of the study is to evaluate the efficacy of MN-166 on muscle strength measured by hand-held dynamometry (HHD), the efficacy of MN-166 on quality of life measured by ALSAQ-5, the efficacy of MN-166 on functional activity measured by ALSFRS-R, the safety and tolerability of MN-166, to characterize the pharmacokinetics (PK) of MN-166 using population PK modeling and to measure survival.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1.Written or verbal informed consent is obtained and willing and able to comply with the protocol in the opinion of the Investigator;
    2.Male or female subjects ages 18 to 80 years, inclusive;
    3.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];
    4.ALS onset of ≤ 18 months from first clinical signs of weakness prior to Screening;
    5.Documented ALS history of location of disease onset (i.e. bulbar onset, limb onset)
    6.A total ALSFRS-R score of at least 35 overall at screening and:
    a.No more than one of the 12 ALSFRS-R individual component items has a score of 1 or less at screening;
    b.For limb onset subjects, ALSFRS-R score of ≥ 3 on item #1 (speech), # 2 (salivation) and # 3 (swallowing);
    7.ALSFRS-R score progression from onset of the first symptom of weakness to the ALSFRS-R score at Screening of > 0.3 points and < 1 point per month calculated as:
    •ALSFRS-R score at Screening minus ALSFRS-R score at onset of first symptom of weakness divided by number of months since onset of first symptom of weakness.
    8.Slow vital capacity ≥ 70% of predicted within at screening;
    9.Currently on a stable dose of riluzole for at least 30 days prior to initiation of study drug;
    10.Females of childbearing potential must use an effective method of contraception throughout the entire study period and for 30 days after study drug discontinuation;
    11.Males should practice contraception (e.g. condom use and contraception by female partner) throughout the entire study period and for 30 days after study drug discontinuation;
    12.Able to swallow study medication capsules;
    13.Subject is willing and able to comply with the protocol assessments and visits, in the opinion of the Investigator;
    14.Has no known allergies to the study drug or its excipients;
    15.Has received pneumococcal vaccine within 6 years prior to starting clinical trial.
    E.4Principal exclusion criteria
    1.Confirmed hepatic insufficiency or abnormal liver function (AST and/or ALT > 3 times the upper limit of normal);
    2.Currently has a clinically significant psychiatric disorder or dementia which would preclude evaluation of symptoms;
    3.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;
    4.Female subject is lactating, pregnant or planning pregnancy at Screening or Baseline;
    5.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;
    6.ALSFRS-R score of ≤ 1 on more than one item in the assessment’s individual components;
    7.Resting pulse < 50 bpm, SA or AV block, uncontrolled hypertension, or repeated demonstration of a QTc interval of > 450 ms;
    8.History of HIV (human immunodeficiency virus), clinically significant chronic hepatitis, or other active infection;
    9.Current use or treated with Edaravone® ≤ 3 months prior to signing consent;
    10.Current use or treated with Nuedexta® ≤ 3 months prior to signing consent;
    11.Current use or treated with Methylcobalamin Vitamin B12 ≤ 3 months prior to signing consent
    12.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;
    13.History of alcohol or substance abuse (DSM-5 criteria) ≤ 3 months prior to screening or alcohol or substance dependence (DSM-5 criteria) ≤ 12 months prior to screening;
    14.Poor peripheral venous access that will limit the ability to draw blood as judged by the Investigator;
    15.Currently participating, or has participated in, a study with an investigational or marketed compound or device ≤ 3 months prior to signing the informed consent;
    16.Unable to cooperate with any study procedures, unlikely to adhere to the study procedures and keep appointments, in the opinion of the Investigator;
    17.Use of tracheostomy, tracheostomy invasive mechanical ventilation [TIMV].
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is the change from baseline in ALSFRS-R score at Month 12 (or last measurement before death in case of censoring) and survival time.
    E.5.1.1Timepoint(s) of evaluation of this end point
    According to the protocol
    E.5.2Secondary end point(s)
    •Mean change from baseline of muscle strength measured by hand-held dynamometry (HHD) at Month 12.
    •Mean change from baseline on quality of life assessed by ALSAQ-5 at Month 12.
    •Mean change from baseline of functional activity measured by ALSFRS-R at Month 12.
    •Responder analysis (%) defined as subjects whose ALSFRS-R was stable or improved over the 12-month Treatment Phase
    •Time to survival as defined by death or permanent dependency to ventilator or tracheostomy.
    •Safety and tolerability 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 monitoring of hematology, blood chemistry, and urine values, measurement of vital signs, ECGs, and medical history, physical and neurological examinations.
    •Relationship between MN-166 plasma levels and ALSFRS-R and adverse events.
    E.5.2.1Timepoint(s) of evaluation of this end point
    According to the protocol
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA19
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Germany
    Greece
    Hungary
    Italy
    Poland
    Spain
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    All subjects who complete the Open-label Phase will be telephoned by a study staff member for a safety follow-up approximately 2 weeks after the last OLE visit (Month 18) to assess adverse event status and to document concomitant medications.
    Subjects who do not participate in the Open-label Extension Phase will be telephoned for a follow-up call approximately 2 weeks after the end of double-blind treatment (Month 12) to document adverse event status and concomitant medications.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months7
    E.8.9.1In the Member State concerned days14
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months7
    E.8.9.2In all countries concerned by the trial days14
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 18
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 2
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 80
    F.4.2.2In the whole clinical trial 230
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Patients will go back to the standard of care at the discretion of the treating PI
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2020-03-11
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-03-02
    P. End of Trial
    P.End of Trial StatusOngoing
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