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    Summary
    EudraCT Number:2021-002251-11
    Sponsor's Protocol Code Number:TPN-101-C9-201
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-10-08
    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 ConcernedSpain - AEMPS
    A.2EudraCT number2021-002251-11
    A.3Full title of the trial
    A Phase 2a Study of TPN-101 in Patients with C9ORF72 ALS/FTD (Amyotrophic Lateral Sclerosis and/or Frontotemporal Dementia)
    Estudio de fase 2a de TPN-101 en pacientes con ELA/DFT C9ORF72 (esclerosis lateral amiotrófica y/o demencia frontotemporal)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A clinical study to learn whether a new drug, TPN-101, is safe when given to patients with amyotrophic lateral sclerosis or frontotemporal dementia due to a genetic mutation called C9orf72 hexanucleotide repeat expansion.
    Un estudio clínico para saber si un nuevo medicamento, TPN-101, es seguro cuando se administra a pacientes con esclerosis lateral amiotrófica o demencia frontotemporal debido a una mutación genética llamada
    expansión repetida de hexanucleótidos C9orf72.
    A.4.1Sponsor's protocol code numberTPN-101-C9-201
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04993755
    A.5.4Other Identifiers
    Name:IND NumberNumber:153073
    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 SponsorTransposon Therapeutics, 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 supportTransposon Therapeutics, Inc
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationTransposon Therapeutics, Inc
    B.5.2Functional name of contact pointAndrew Satlin
    B.5.3 Address:
    B.5.3.1Street Address2765 Sand Hill Road c/o Canaan Partners
    B.5.3.2Town/ cityMenlo Park, CA
    B.5.3.3Post code94025
    B.5.3.4CountryUnited States
    B.5.4Telephone number19494229676
    B.5.5Fax number18772253670
    B.5.6E-mailasatlin@transposonrx.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.3.1Product nameTPN-101
    D.3.2Product code TPN-101
    D.3.4Pharmaceutical form Capsule, hard
    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 INNCENSAVUDINE
    D.3.9.1CAS number 634907-30-5
    D.3.9.2Current sponsor codeTPN-101
    D.3.9.4EV Substance CodeSUB33640
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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, hard
    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 or frontotemporal dementia due to a genetic mutation called C9orf72 hexanucleotide repeat expansion
    Esclerosis lateral amiotrófica o demencia frontotemporal debido a una
    mutación genética llamada expansión de repetición de hexanucleótidos
    C9orf72
    E.1.1.1Medical condition in easily understood language
    Amyotrophic lateral sclerosis or frontotemporal dementia due to a genetic mutation called C9orf72 hexanucleotide repeat expansion
    Esclerosis lateral amiotrófica o demencia frontotemporal debido a una
    mutación genética llamada expansión de repetición de hexanucleótidos
    C9orf72
    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.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10068968
    E.1.2Term Frontotemporal dementia
    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
    To assess the safety and tolerability of TPN-101 in patients with C9ORF72 ALS/FTD
    Evaluar la seguridad y tolerabilidad de TPN-101 en pacientes con
    C9ORF72 ELA / DFT
    E.2.2Secondary objectives of the trial
    • To assess the concentrations of TPN-101 in plasma and cerebrospinal fluid (CSF)
    • To assess target engagement of TPN-101 in blood
    • To assess disease-related biomarkers
    • To assess the PD effects of TPN-101 in blood and CSF
    • To assess inflammatory biomarkers in blood and/or CSF
    • To assess clinical and functional status
    • To assess survival
    • Evaluar las concentraciones de TPN-101 en plasma y líquido
    cefalorraquídeo (LCR)
    • Evaluar la interacción con la diana de TPN-101 en sangre
    • Evaluar los biomarcadores relacionados con la enfermedad
    • Evaluar los efectos farmacodinámicos (FD) de TPN-101 en sangre y
    LCR
    • Evaluar los biomarcadores inflamatorios en sangre y/o LCR
    • Evaluar el estado clínico y funcional
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Males or females ≥ 18 years of age at the time of informed consent
    2. Have documentation of a clinical genetic test demonstrating the presence of a confirmed repeat expansion in the C9orf72 gene from a CLIA certified laboratory
    3. Body weight range of ≥ 41 kg (90 lbs) to ≤ 118 kg (260 lbs)
    4. Score ≥ 18 on the Mini-Mental State Exam (MMSE) at Screening
    5. If female, must be postmenopausal (for at least 2 years), surgically sterilized (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), or agree to use highly effective methods of contraception from Screening through Week 52
    6. If male, with a partner who is not postmenopausal (for at least 2 years) or surgically sterilized (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), the patient must agree that he and his partner will use highly effective methods of contraception from Screening through Week 52
    7. Able to perform all protocol-specified assessments, including neuropsychological tests; and comply with taking study medication and the study visit schedule, as judged by the investigator
    8. Have a reliable caregiver to accompany the patient to all study visits. Caregiver must be able to read, understand, and speak local language fluently to ensure comprehension of informed consent and informant-based assessments of the patient. Caregiver must also have frequent contact with patient (at least 3 hours per week at one time or at different times) and be willing to monitor the patient's health and concomitant medications throughout the study
    9. Able to understand and provide written informed consent at Screening
    10. Agree to allow data sharing across observational longitudinal and interventional studies using an encrypted global unique identifier (GUID) so that potential prior or future data on biomarkers and disease progression can be made accessible to the sponsor
    11. Stable doses of all concomitant medications for 1 month prior to Screening (e.g., edaravone, riluzole, dextromethorphan/quinidine, psychotropic medications, cognitive enhancers, etc.)

    For patients with ALS (with or without FTD):
    12. Diagnosis of ALS (probable, possible, laboratory-supported probable or definite) according to the World Federation of Neurology revised E1 Escorial criteria
    13. Onset of weakness within 3 years prior to Screening
    14. SVC ≥ 60% of predicted normal adjusted for sex, age, and height (from the sitting position)
    15. Able to perform reproducible pulmonary function tests
    16. ALSFRS-R ≥ 30 at Screening

    For patients with FTD:
    17. A gradual, progressive decline in behavior, language, or motor function consistent with C9orf72 hexanucleotide expansion-related syndrome such as behavioral variant FTD, primary progressive aphasia, or amnestic syndrome
    18. CDR plus NACC FTLD global score of 0.5-2.0 at Screening
    1. Hombres o mujeres ≥ 18 años de edad en el momento del
    consentimiento informado
    2. Disponer de documentación de una prueba genética clínica que demuestre la presencia de una expansión repetida confirmada en el gen C9orf72 de un laboratorio certificado por la CLIA.
    3. Rango de peso corporal de ≥ 41 kg (90 lbs) a ≤ 118 kg (260 lbs)
    4. Puntuación ≥ 18 en el Mini Examen del Estado Mental (Mini-Mental State Exam, MMSE) en la fase de selección
    5. Si es mujer, deberá ser posmenopáusica (desde hace al menos 2
    años), estar esterilizada quirúrgicamente (ligadura de trompas bilateral, ooforectomía bilateral o histerectomía) o deberá utilizar métodos anticonceptivos muy eficaces desde la fase de selección hasta la semana 52
    6. Si es varón y tiene una pareja que no sea posmenopáusica (desde
    hace al menos 2 años) ni esté esterilizada quirúrgicamente (ligadura de trompas bilateral, ooforectomía bilateral o histerectomía), el paciente y su pareja deberán utilizar métodos anticonceptivos altamente eficaces desde la fase de selección hasta la semana 52
    7. Ser capaz de realizar todas las evaluaciones especificadas en el
    protocolo, incluidas las pruebas neuropsicológicas; y cumplir con la toma del medicamento en estudio y el programa de visitas del estudio, a criterio del investigador
    8. Tener un cuidador fiable que acompañe al paciente a todas las visitas del estudio. El cuidador debe ser capaz de leer, entender y hablar el idioma local con fluidez para garantizar la comprensión del
    consentimiento informado y las evaluaciones del paciente por parte del informante. El cuidador también deberá tener contacto frecuente con el paciente (al menos 3 horas por semana, ya sean seguidas o no) y estar dispuesto a supervisar la salud del paciente y la medicación
    concomitante durante todo el estudio
    9. Ser capaz de entender y dar el consentimiento informado por escrito durante la fase de selección
    10. Aceptar que se compartan los datos de los estudios longitudinales
    de observación y de intervención mediante un identificador global único
    (GUID, por sus siglas en inglés) encriptado, de modo que el promotor
    pueda acceder a los posibles datos anteriores o futuros sobre los
    biomarcadores y la evolución de la enfermedad.
    11. Dosis estables de todos los medicamentos concomitantes durante 1
    mes antes de la fase de selección (por ejemplo, edaravona, riluzol,
    dextrometorfano/quinidina, medicamentos psicotrópicos, potenciadores cognitivos, etc.) En pacientes con ELA (con o sin DFT):
    12. Diagnóstico de ELA (probable, posible, probable o seguro con apoyo de pruebas de laboratorio) según los criterios revisados de El Escorial modificados por la Federación Mundial de Neurología
    13. Inicio de debilidad en los 3 años anteriores a la fase de selección
    14. Capacidad vital lenta (CVL) ≥ 60% de la normal predicha ajustada
    por sexo, edad y altura (en posición sentada)
    15. Capaz de realizar pruebas de función pulmonar reproducibles
    16. Escala Revisada de Valoración Funcional de la ELA (ALSFRS-R) ≥ 30
    en la fase de selección en pacientes con DFT:
    17. Un empeoramiento gradual y progresivo del comportamiento, el
    lenguaje o la función motora compatible con el síndrome relacionado con la expansión del hexanucleótido C9orf72, como la variante conductual de la DFT, la afasia primaria progresiva o el síndrome amnésico
    18. Instrumento de Clasificación de la Demencia CDR y Dominios de
    Conducta y Lenguaje del Centro Nacional de Coordinación del Alzheimer (CDR plus NACC FTLD): puntuación global de 0,5-2,0 en la fase de selección
    E.4Principal exclusion criteria
    1. Presence of other significant neurological or psychiatric disorders including (but not limited to) biomarker confirmed Alzheimer's disease; dementia with Lewy bodies; prion disease; Parkinson's disease; multiple sclerosis; a primary or severe psychotic disorder; severe bipolar or unipolar depression; prior history of suicidal thoughts or behavior that are believed to represent a current safety risk; seizure; brain tumor or other space-occupying lesion; history of stroke; or history of severe head injury within the past 20 years
    2. History of significant brain abnormality, including, but not limited to, prior hemorrhage or infarct, cerebral contusion, encephalomalacia, aneurysm, vascular malformation, subdural hematoma, hydrocephalus, space-occupying lesion (e.g., abscess or brain tumor such as meningioma); symptoms or signs of elevated intracranial pressure, e.g., symptoms or history of head injury or abnormal funduscopic exam. If there is history or evidence on neurologic exam suggesting possible subdural hematoma (SDH), patients should be fully evaluated, including magnetic resonance imaging (MRI) if indicated, to exclude significant, new SDH
    3. Active alcohol, drug abuse or substance abuse, or any other reason that makes it unlikely that the patient will comply with study procedures in the opinion of the investigator
    4. Clinically significant findings on Screening laboratory testing, physical examination or vital signs that are not specific to ALS/FTD that could interfere with the conduct of the study, the interpretation of the data, or increase patient risk
    5. Clinically significant intercurrent illness or medical condition (e.g., hematological, endocrine, cardiovascular, renal, hepatic, or gastrointestinal disease) that would jeopardize the safety of the patient, limit participation, or compromise the interpretation of the data derived from the patient
    6. History of HIV infection, hepatitis B or hepatitis C, or any active infection
    7. History of cancer within 5 years of Screening, with the exception of fully excised non-melanoma skin cancers
    8. Receipt of an investigational agent within 30 days or 5 half-lives prior to Screening, whichever is longer
    9. Prior treatment with any monoclonal antibody within 6 months of Screening
    10. Receipt of systemic corticosteroids within 30 days prior to Screening
    11. Any vaccination within 30 days prior to study drug administration
    12. Has smoked or used tobacco products within 6 months prior to study drug administration
    13. Hypertension, defined as confirmed systolic blood pressure (SBP) > 170 mmHg and/or diastolic blood pressure (DBP) > 100 mmHg at Screening
    14. Hypotension, defined as confirmed SBP < 90 mmHg and/or DBP < 60 mmHg at Screening
    15. Any major surgery within 4 weeks of Screening
    16. Females who are pregnant (positive pregnancy test at Screening or prior to administration of study drug), breastfeeding, or unable or unwilling to use highly effective methods of contraception throughout the study
    17. Contraindication to undergoing a lumbar puncture (LP) including, but not limited to: inability to tolerate an appropriately flexed position for the time necessary to perform an LP; international normalized ratio (INR) > 1.4 or other coagulopathy; platelet count of < 120,000/μL; infection at the desired LP site; taking anti-platelet or anti-coagulant medication within 30 days of Screening (Note: aspirin is permitted); severe degenerative arthritis of the lumbar spine; suspected non-communicating hydrocephalus or intracranial mass; prior history of spinal mass or trauma
    18. Allergy to any of the components of the study drug
    19. History of any significant drug allergy (such as anaphylaxis or hepatotoxicity)
    20. Physical and laboratory test findings, including the following:
    a. Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG, or clinical laboratory determinations beyond what is consistent with the target population
    b. Clinically significant abnormality on 12-lead ECG prior to study drug administration, confirmed by repeat testing
    c. Total bilirubin, alanine aminotransferase (ALT), or aspartate aminotransferase (AST) > 2 × upper limit of normal (ULN), confirmed by repeat testing
    d. Serum creatinine > 168μmol/L (1.9mg/dL), confirmed by repeat testing
    e. Hematocrit < 35% for males and < 32% for females, absolute neutrophil cell count of < 1500/μL
    f. Clinically significant abnormal thyroid stimulating hormone (TSH) test
    g. Abnormally increased number of white blood cells (> 7 cells/mm3) in the CSF obtained at the Screening Visit; if there is evidence that the spinal tap was traumatic, patients with > 7 cells/mm3 must be discussed with the medical monitor to determine if they may be eligible
    h. Hemoglobin A1C >7%, confirmed by repeat testing
    i. Positive blood screen for HIV, hepatitis C antibody, or hepatitis B surface antigen
    1.Presencia de otros trastornos neurológicos o psiquiátricos
    significativos, incluyendo (entre otros): enfermedad de Alzheimer
    confirmada por biomarcadores; demencia con cuerpos de Lewy;
    enfermedad por priones; enfermedad de Parkinson; esclerosis múltiple; un trastorno psicótico primario o grave; depresión bipolar o unipolar grave; antecedentes de pensamientos o comportamientos suicidas que se consideren un riesgo de seguridad actual; convulsiones; tumor cerebral u otra lesión que ocupe espacio; antecedentes de ictus oantecedentes de traumatismo craneal grave en los últimos 20 años.
    2.Antecedentes de anomalías cerebrales significativas, incluyendo, entre otras: hemorragia o infarto previos, contusión cerebral, encefalomalacia, aneurisma, malformación vascular, hematoma subdural, hidrocefalia, lesión que ocupe espacio (por ejemplo, absceso o tumor cerebral como un meningioma); síntomas o signos de presión intracraneal elevada, por ejemplo, síntomas o antecedentes de traumatismo craneal o exploración
    anormal del fondo de ojo. Si existen antecedentes o pruebas en la
    exploración neurológica que indiquen que hay un posible hematoma
    subdural (HSD), los pacientes deberán someterse a una evaluación
    completa, incluyendo una resonancia magnética (RM) si así está
    indicado, para descartar una nueva HSD significativa
    3. Abuso activo de alcohol, drogas o sustancias, o cualquier otra razón por la que sea improbable que el paciente cumpla con los procedimientos del estudio, según el criterio del investigador
    4. Hallazgos clínicamente significativos en las pruebas analíticas de la
    fase de selección, en la exploración física o en las constantes vitales que no sean específicos de ELA/DFT y que puedan interferir con la
    realización del estudio, la interpretación de los datos o aumentar el
    riesgo para el paciente
    5. Enfermedad o afección médica intercurrente clínicamente significativa (por ejemplo, enfermedad Hematológica, endocrina, cardiovascular, renal, hepática o gastrointestinal) que pueda poner en peligro la seguridad del paciente, limitar su participación o comprometer la interpretación de los datos derivados del mismo
    6.Antecedentes de infección por el virus de inmunodeficiencia humana (VIH), hepatitis B o hepatitis C, o cualquier infección activa
    7.Antecedentes de cáncer en los 5 años anteriores a la fase de selección, a excepción de los cánceres de piel distintos del melanoma y extirpados de forma completa
    8.Recepción de un agente en investigación dentro de los 30 días o 5
    semividas anteriores a la fase de selección, lo que sea más largo
    9.Tratamiento previo con cualquier anticuerpo monoclonal dentro de los 6 meses anteriores a la fase de selección
    10.Recepción de corticosteroides sistémicos en los 30 días anteriores a la fase de selección
    11. Cualquier vacuna en los 30 días anteriores a la administración del
    medicamento en estudio 12.Haber fumado o consumido productos de tabaco en los 6 meses anteriores a la administración del medicamento enestudio
    13.Hipertensión, definida como presión arterial sistólica (PAS) > 170
    mmHg y/o presión arterial diastólica (PAD) > 100 mmHg confirmadas en la fase de selección
    14.Hipotensión, definida como PAS < 90 mmHg y/o PAD < 60 mmHg
    confirmadas en la fase de selección
    15.Cualquier cirugía mayor dentro de las 4 semanas anteriores a la fase de selección
    16.Mujeres embarazadas (prueba de embarazo positiva en la fase de
    selección o antes de la administración del medicamento en estudio), en periodo de lactancia, o que no puedan o no quieran utilizar métodos anticonceptivos muy eficaces durante el estudio
    17.Contraindicación para someterse a una punción lumbar (PL),
    incluyendo, entre otras: incapacidad para tolerar una posición
    adecuadamente flexionada durante el tiempo necesario para realizar una PL; cociente internacional normalizado (INR) > 1,4 u otra coagulopatía; recuento de plaquetas < 120.000/μl; infección en el zona deseada para la PL; toma de medicamentos antiplaquetarios o anticoagulantes en los 30 días anteriores a la fase de selección (Nota: está permitida la aspirina); artritis degenerativa grave de la columna lumbar; sospecha de hidrocefalia no comunicante o masa intracraneal; antecedentes de masa o traumatismo vertebral.
    18. Alergia a cualquiera de los componentes del medicamento en estudio
    19.Antecedentes de cualquier alergia significativa a medicamentos
    (como anafilaxia o hepatotoxicidad)
    20.Hallazgos de las pruebas físicas y analíticas sanguíneas.
    E.5 End points
    E.5.1Primary end point(s)
    Incidence and severity of treatment-emergent adverse event (TEAEs) of TPN-101 administered for up to 48 weeks in patients with C9ORF72 ALS/FTD
    Incidencia y gravedad de los AAST del TPN-101 administrado hasta 48
    semanas en pacientes con ELA/DFT C9ORF72
    E.5.1.1Timepoint(s) of evaluation of this end point
    48 weeks
    48 semanas
    E.5.2Secondary end point(s)
    • Concentrations of TPN-101 in plasma and cerebrospinal fluid (CSF)
    • Target engagement of TPN-101 in blood as measured by LINE-1 (L1) complementary DNA (cDNA)
    • Disease-related biomarkers
    • Disease modification-related neuro-biomarkers, including neurofilament light chain (NfL) and neurofilament heavy chain (pNfH) in blood and CSF
    • Inflammatory biomarkers in blood and/or CSF
    • Clinical and functional status, as measured by ALS Functional Rating Scale-Revised (ALSFRS-R), ALS Assessment Questionnaire-40 item (ALSAQ-40), slow vital capacity (SVC), CDR Dementia Staging Instrument plus National Alzheimer's Coordinating Center Behavior and Language Domains -sum of boxes (CDR plus NACC FTLD-SB), frontotemporal dementia (FTD) Rating Scale, Color Trails, Stroop Color and Word Test, Montreal Cognitive Assessment (MoCA), cortical basal ganglia functional scale (CBFS), Center for Neurologic Study – Bulbar Function Scale (CNS-BFS), ALS Cognitive Behavioral Scale (ALS-CBS), and Neuropsychiatric Inventory–Questionnaire (NPI-Q)
    • Survival
    • Other safety assessments, including clinically significant changes in physical examinations, neurological examinations, vital sign measurements, body weight, clinical laboratory tests, electrocardiograms (ECGs), and assessments of suicidality (i.e., C-SSRS)
    • Concentraciones de TPN-101 en plasma y LCR
    • Interacción con la diana del TPN-101 en sangre medida por el ADNc
    de L1
    • Biomarcadores relacionados con la enfermedad
    • Neurobiomarcadores relacionados con la modificación de la
    enfermedad, incluyendo NfL y pNfH en sangre y LCR
    • Biomarcadores inflamatorios en sangre y/o LCR
    • Estado clínico y funcional, medido por: ALSFRS-R, ALSAQ-40, la CVL,
    CDR plus NACC FTLD-SB, la Escala de Calificación de la DFT, el Test de
    Colores, el Test Stroop de Colores y Palabras, MoCA, CBFS, CNS-BFS,
    ALS-CBS Y NPI-Q.
    • Supervivencia
    Otras evaluaciones de seguridad, incluyendo los cambios clínicamente significativos en las exploraciones físicas, las exploraciones neurológicas, las mediciones de constantes vitales, el peso corporal, las pruebas clínicas de laboratorio, los ECG y las evaluaciones del riesgo de suicidio (es decir, C-SSRS)tests.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Week 48 and monitored throughout the study
    Semana 48 y monitorizado durante todo el estudio
    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 Yes
    E.6.13.1Other scope of the trial description
    Disease-related biomarkers
    Survival
    Biomarcadores relacionados con enfermedades
    Supervivencia
    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 No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    parte 1 período doble ciego de 24 semanas luego viene parte 2 etiqueta abierta en sem 25 para todos
    Part 1 is double blind period of 24 weeks followed by part 2 (open label) at week 25 for all patient
    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 EEA10
    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
    Canada
    United States
    Belgium
    France
    Germany
    Netherlands
    Spain
    United Kingdom
    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
    Ultimo Paciente, Ultima Visita
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months1
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months1
    E.8.9.2In all countries concerned by the trial days0
    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: 10
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 10
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Based upon the judgement of Investigator, in case the patient will not be able to understand and sign the informed consent, then Investigator will ensure that consent must be obtained from a legal representative, if applicable to this study.
    Según el criterio del investigador, en caso de que el paciente no pueda
    comprender y firmar el consentimiento informado, el investigador se
    asegurará de que se obtenga el consentimiento de un representante
    legal, si corresponde a este estudio.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 20
    F.4.2.2In the whole clinical trial 40
    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)
    None
    No hay
    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 Decision2022-01-31
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-01-24
    P. End of Trial
    P.End of Trial StatusOngoing
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