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    Summary
    EudraCT Number:2016-001696-79
    Sponsor's Protocol Code Number:KH176-201
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2016-08-18
    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 ConcernedNetherlands - Competent Authority
    A.2EudraCT number2016-001696-79
    A.3Full title of the trial
    A double-blind, randomized, placebo-controlled, single-center, two-way cross-over study with KH176 in patients with the mitochondrial DNA tRNALeu(UUR) m.3243A>G mutation and clinical signs of mitochondrial disease
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase II study with KH176 in patients with mitochondrial disease
    A.3.2Name or abbreviated title of the trial where available
    The KHENERGY study
    A.4.1Sponsor's protocol code numberKH176-201
    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 SponsorKhondrion BV
    B.1.3.4CountryNetherlands
    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 supportKhondrion BV
    B.4.2CountryNetherlands
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationKhondrion BV
    B.5.2Functional name of contact pointEdwin Spaans, CMO
    B.5.3 Address:
    B.5.3.1Street AddressPhilips van Leydenlaan 15
    B.5.3.2Town/ cityNijmegen
    B.5.3.3Post code6525 EX
    B.5.3.4CountryNetherlands
    B.5.4Telephone number31654997700
    B.5.6E-mailspaans@khondrion.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/3/14/1336
    D.3 Description of the IMP
    D.3.1Product nameKH176
    D.3.2Product code KH176
    D.3.4Pharmaceutical form Oral liquid
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    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 placeboOral liquid
    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
    Inherited mitochondrial disease, including MELAS (mitochondrial Encephalopathy Lactic Acidosis and Stroke like episodes) and MIDD (Maternally Inherited Diabetes and Deafness)
    E.1.1.1Medical condition in easily understood language
    Inherited mitochondrial diseases
    E.1.1.2Therapeutic area Diseases [C] - Nutritional and Metabolic Diseases [C18]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the effect of KH176 on gait (Gaitrite®) parameters: step-length and variability in step-time and step-width in patients with a m.3243A>G mutation
    E.2.2Secondary objectives of the trial
    - To explore the effect of KH176 on biomarkers of mitochondrial functioning in patients with an m.3243A>G mutation.
    - To explore the effect of KH176 on functional clinical measures of mitochondrial disease in patients with an m.3243A>G mutation.
    - To investigate the tolerability and safety of KH176 following 28 days of oral administration to patients with an m.3243A>G mutation.
    - To investigate the multiple dose pharmacokinetics of KH176 following 28 days of oral administration in patients with an m.3243A>G mutation
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Participants in the trial will be patients with a mitochondrial DNA tRNALeu(UUR) m.3243A>G mutation and clinical signs of mitochondrial disease, including but not limited to MELAS, MIDD and mixed types.
    E.4Principal exclusion criteria
    1. Motoric abnormalities other than related to the mitochondrial disease interfering with the outcome parameters.
    2. CPEO patients with clinical signs and symptoms restricted to the eye only
    3. Heteroplasmy level as measured in urine < 20%
    4. Poor nutritional state as judged by the investigator
    5. Body Mass Index (BMI) not within 18.0-30.0 kg/m2 at screening.
    6. History of cancer
    7. Surgery or active illness of gastro-intestinal tract that might interfere with absorption.
    8. Participation in a trial of an investigational product in the preceding 3 months prior to the first dose or during this trial.
    9. Positive drug, alcohol or cotinine test at screening and/or admission (Day 1 of the first dosing period).
    10. Clinically relevant abnormal laboratory, ECG recordings, cardiac echo (within 1 year prior to screening), vital signs or physical or mental findings at screening as judged by the Investigator.
    11. Clinically relevant abnormal ECG or cardiac functioning as judged by a cardiologist.
    12. ECG: QTc > 450 ms, abnormal T-wave
    13. Symptomatic heart failure or signs of ischemic heart disease
    14. Left Ventricular Ejaction Fraction <45%
    15. History or family history of congenital Long QT syndrome
    16. Increased or decreased potassium (local laboratory normal range)
    17. Inadequate contraception use, pregnancy or breast feeding (females)
    18. Clinically significant presence or history of allergy as judged by the Investigator.
    19. History of hypersensitivity or idiosyncrasy to any of the components of the investigational drug.
    20. Within 4 weeks prior to dosing, the use of (multi)vitamins, co-enzyme Q10, Vitamine E, riboflavin, and anti-oxidant supplements (and idebenone/EPI-743), as well as any medication negatively influencing mitochondrial functioning (including but not limited to valproic acid, glitazones, statins, anti-virals, amiodarone, and NSAID’s) as well as any strong Cytochrome P450 inhibitors (all ‘conazoles-anti-fungals’, HIV antivirals, grapefruit) and strong Cytochrome P450 inducers (a.o. carbamazepine, phenobarbital, phenytoin, rifampicine, St Johns wort, pioglitazone, troglitazone) as well as any medication known to affect cardiac repolarization (all anti-psychotics, several anti-depressants: nor/amytriptilline, fluoxetine, anti-emetics: domperidone (motilium) granisetron, ondansetron)
    E.5 End points
    E.5.1Primary end point(s)
    Gait parameters: cadence, walking speed, right and left step and stride lengths, and right and left step times
    E.5.1.1Timepoint(s) of evaluation of this end point
    baseline and after 28 days
    E.5.2Secondary end point(s)
    - Safety parameters, including cardiovascular
    - Pharmacokinetic parameters
    - Pharmacodynamic parameters (metabolome, oxidative platform, glutathione, FGF21, GDF12, PRDX1)
    - NMDAS Score
    - Spirometric parameters: Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 sec (FEV1), Peak Expiratory Flow (PEF), Maximal inspiratory mouth pressure (MIP), Maximal Expiratory mouth pressure (MEP)
    - 30-Seconds sit – stand test: Number of standings.
    - Handgrip dynamometry: Maximum grip strength
    - 6 Minutes Chewing test: VAS pain, VAS tiredness, Rate of Mastication, quality of movement
    - 6 Minutes Walk Test (during the gait evaluation): Distance
    - RAND-SF36 score
    - Hospital Anxiety and Depression Scale (HAD), supplemented with a Beck Depression Index (BDI)
    - Checklist Individual Strenght (CIS)
    - Test of Attentional Performance (TAP): Alertness and Mental Flexibility
    E.5.2.1Timepoint(s) of evaluation of this end point
    Safety parameters continuously and several assessements during treatment
    Pharmacokinetics on Day 1 and 28
    Other assessments at baseline and after 28 days
    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 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) 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) No
    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 Yes
    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 Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee No
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months7
    E.8.9.1In the Member State concerned days
    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: 20
    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 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.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)
    Normal treatment of condition
    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 Decision2016-08-18
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-09-06
    P. End of Trial
    P.End of Trial StatusOngoing
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