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    The EU Clinical Trials Register currently displays   42869   clinical trials with a EudraCT protocol, of which   7063   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2014-002053-19
    Sponsor's Protocol Code Number:CLMI070X2201
    National Competent Authority:Hungary - National Institute of Pharmacy
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2018-07-17
    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 number2014-002053-19
    A.3Full title of the trial
    An open-label multi-part first-in-human study of oral LMI070 in infants with Type 1 spinal muscular atrophy
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Clinical trial of LMI070 given by mouth to Type I SMA infant patients.
    Az orális LMI070 nyílt, több részből álló, első humán vizsgálata 1-es típusú spinális izomatrófiában szenvedő csecsemőknél
    A.3.2Name or abbreviated title of the trial where available
    CLMI070X2201
    A.4.1Sponsor's protocol code numberCLMI070X2201
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02268552
    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 SponsorNovartis Pharma Services AG
    B.1.3.4CountrySwitzerland
    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 supportNovartis Pharma Services AG
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationNovartis Hungary Kft.
    B.5.2Functional name of contact pointPublic Information Desk
    B.5.3 Address:
    B.5.3.1Street AddressBartók Béla út 43-47
    B.5.3.2Town/ cityBudapest
    B.5.3.3Post code1114
    B.5.3.4CountryHungary
    B.5.4Telephone number00 36 1 457-6500
    B.5.5Fax number00 36 1 457-6600
    B.5.6E-mailinfoph.hungary@novartis.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 No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.2Product code LMI070
    D.3.4Pharmaceutical form Oral solution
    D.3.4.1Specific paediatric formulation Yes
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.3Other descriptive nameLMI070
    D.3.9.4EV Substance CodeSUB166489
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number3.5
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Spinal Muscular Atrophy
    E.1.1.1Medical condition in easily understood language
    motor neuron disease
    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 20.1
    E.1.2Level LLT
    E.1.2Classification code 10051203
    E.1.2Term Spinal muscular atrophy congenital
    E.1.2System Organ Class 100000004850
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Part 1: Determine the safety and tolerability of ascending weekly doses and estimate the MTD of branaplam in infants with Type 1 SMA.
    Part 2: Evaluate the safety and tolerability of ascending weekly doses of branaplam for 52 weeks in patients with Type 1 SMA.
    E.2.2Secondary objectives of the trial
    Part 1:
    - To evaluate branaplam pharmacokinetics in plasma after single and repeated doses of branaplam.
    - To evaluate the effect of branaplam on growth parameters
    - To evaluate the effect of branaplam on respiratory function
    - To evaluate the effect of branaplam on infant motor development

    In addition to the above for Part 2:
    - To evaluate the efficacy of branaplam on motor and developmental milestones
    - To evaluate the efficacy of branaplam on the ability to sit without support.
    - To evaluate the efficacy of LMI070 on ulnar and peroneal nerve compound motor action potential [CMAP]
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Common for both Parts 1 and 2:
    - Type 1 SMA, diagnosed clinically, with symptom onset <6 months of age and genetic confirmation of mutations in both alleles of the SMN1 gene, and with SMN2 copy number of 2.
    - Best supportive care in place and stable for at least 14 days before screening.
    - Must be able to demonstrate antigravity strength in both biceps. At birth gestational age >32 weeks and body weight at birth >2 kg.
    - Must live within 2 hours drive of study center. Clearance should be obtained from the site investigator and sponsor if the patient
    resides more than 2 hours ground travel from the study center

    Specific for Part 1
    - Age at screening between 1 and 7 months
    - Must have or agree to have placement of feeding tube for enteral access via nasogastric (NG), nasojejunal (NJ), percutaneous
    gastrostomy (PEG), or percutaneous jejunostomy (PEJ) tube for administration of branaplam (for patients in whom branaplam
    cannot be administered orally ; NG tube may be removed between doses).

    Specific for Part 2
    - Age at screening between 30 and 180 days of age
    - Must have or agree to have placement of feeding tube for enteral access via nasogastric (NG), nasojejunal (NJ), percutaneous
    gastrostomy (PEG), or percutaneous jejunostomy (PEJ) tube for administration of branaplam (for the first administration only and for patients in whom branaplam cannot be administered orally; NG tube may be removed between doses).
    - Minimum CHOP INTEND score of 15 at baseline
    - Must be able to feed orally for all nutritional needs and be greater than the 2nd percentile for weight on the standard growth curves for the country of origin
    E.4Principal exclusion criteria
    Common for both Parts 1 and 2:
    - Neurologic, or neuromuscular conditions other than SMA.
    - Anemia, leukopenia, neutropenia or thrombocytopenia
    - Hepatic dysfunction
    - Age adjusted renal dysfunction
    - Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy at any time during the screening period.
    - Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy at any time during the screening period.
    - Excluding SMA, any medically unstable condition including cardiomyopathy, hepatic dysfunction, kidney disorder, endocrine disorder, GI disorders, prematurity of <32 weeks gestation, metabolic disorders, severe respiratory compromise and significant brain abnormalities or injuries including hypoxic-ischemic encephalopathy.
    - Current diagnosis of cardiac and/or vascular abnormalities or ECG abnormalities
    - Acute or ongoing medical condition that, according to the Site Investigator and discussed with sponsor, would interfere with the conduct and assessments of the study. Examples are medical disability other than SMA that would interfere with the assessment of safety or would compromise the ability of the subject to undergo study procedures including be assessed by CHOP INTEND motor scale, changes in hematologic parameters or gastrointestinal dysfunction that would compromise the ability of adequate assessment of safety

    Specific for Part 1
    - Use of other investigational drugs within 14 days.
    - Intractable seizure disorder (other than inactive febrile seizures).
    - Persistent (in the opinion of the Investigator) hypoxemia (O2 saturation awake <92% or O2 saturation asleep <91%, without ventilation support) or requiring oral suctioning >2 per day, or presence of a tracheostomy.

    Specific for Part 2
    - Use of gene transfer at any time or other investigational drugs within 14 days.
    - Patients who have received nusinersen at any time prior to screening
    - Intractable epilepsy
    - Persistent (in the opinion of the Investigator) hypoxemia (O2 saturation awake <92% or O2 saturation asleep <91%, without ventilation support), or presence of a tracheostomy.
    E.5 End points
    E.5.1Primary end point(s)
    Part 1 Safety & Tolerability [Time Frame: 13 Weeks]:
    To evaluate the effect of branaplam on the following;
    - Number of adverse events reported at all dose levels
    - Changes from baseline in existing and newly reported findings on physical examination
    - Changes from baseline in hematology, blood chemistry and urinalysis results at all dose levels
    - Changes from baseline in vital signs at all dose levels
    - Changes from baseline on existing or newly reported ophthalmologic findings at all dose levels
    - Changes from baseline on existing or newly reported cardiac function at all dose levels
    - Changes from baseline in existing and newly reported neurological findings at all dose levels
    - Changes from baseline in existing and newly reported neurophysiological findings at all dose levels

    Part 2 Safety & Tolerability [Time Frame: 52Weeks]:
    To evaluate the effect of branaplam on the following;
    - Number of adverse events reported at all dose levels
    - Changes from baseline in existing and newly reported findings on physical examination
    - Changes from baseline in hematology, blood chemistry and urinalysis results at all dose levels
    - Changes from baseline in vital signs at all dose levels
    - Changes from baseline on existing or newly reported ophthalmologic findings at all dose levels
    - Changes from baseline on existing or newly reported cardiac function at all dose levels
    - Changes from baseline in existing and newly reported neurological findings at all dose levels
    - Changes from baseline in existing and newly reported neurophysiological findings at all dose levels
    E.5.1.1Timepoint(s) of evaluation of this end point
    See Above
    E.5.2Secondary end point(s)
    Part 1:
    - Changes in Growth Parameters from baseline [Time Frame: Screening, Day 1, Day 8 to Day 85. Extended treatment periods: every 4 weeks and at the End of Study]
    - Changes in respiratory function from baseline [Time Frame: Baseline, Day 8 to Day 85. Extended treatment periods: every 4 weeks and at the End of Study]
    - Changes in Infant motor development from baseline [Time Frame: Baseline, Day 36, Day 85. Extended treatment periods: every 6 to 7 weeks and at the End of Study]
    - Collect pharmacokinetic data from single and repeated dosing [Time Frame: Parts 1 and 2: Day 1 (Pre-dose + 1, 2, 4, 8 & 24 hours post-dose), Days 2, 3, 5, 8, 29. Part 1: Day 43. Part 2: Day 57, 57, 92 (Predose + 4 & 24 hours post-dose), 94, 99, 274 (Pre-dose + 4 & 24 hours post-dose), 276, 281]

    In addition to the above for Part 2:
    - Changes in motor and developmental milestones from baseline [Time Frame: Baseline, Day 15, Day 36, Day 57, Day 88 + End of Study]
    - Changes in Ulnar Nerve Compound Motor Action Potential (CMAP) from baseline [Time Frame: Baseline, Day 88 + End of Study]
    - Changes from baseline on the ability to site without support [Time Frame: 52 weeks]
    E.5.2.1Timepoint(s) of evaluation of this end point
    See above
    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 Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    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) Yes
    E.7.1.1First administration to humans Yes
    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) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    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 No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA15
    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
    Belgium
    Bulgaria
    Czech Republic
    Denmark
    Germany
    Hungary
    Italy
    Poland
    Russian Federation
    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
    When the last subject completes their End of Study visit, and any repeat assessments associated with this visit have been documented and followed-up appropriately by the Investigator, or in the event of an early study termination decision, the date of that decision.
    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 months1
    E.8.9.1In the Member State concerned days28
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months4
    E.8.9.2In all countries concerned by the trial days4
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 44
    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) Yes
    F.1.1.4.1Number of subjects for this age range: 44
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) No
    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 No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    infants
    F.3.3.7Others Information not present in EudraCT
    F.4 Planned number of subjects to be included
    F.4.1In the member state2
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 44
    F.4.2.2In the whole clinical trial 44
    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 initially be dosed for 13 weeks, however dosing may be extended if recommended by the independent DMC.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2018-09-17
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-09-07
    P. End of Trial
    P.End of Trial StatusCompleted
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