Stránka klinických studií Nct

Summary
EudraCT Number:2020-004708-32
Sponsor's Protocol Code Number:232SM302
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:2021-02-09
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
A. Protocol Information
A.1Member State ConcernedSpain - AEMPS
A.2EudraCT number2020-004708-32
A.3Full title of the trial
A Long-Term Extension Study of Nusinersen (BIIB058) Administered at Higher Doses in Participants With Spinal Muscular Atrophy Who Previously Participated in an Investigational Study With Nusinersen
Estudio de extensión a largo plazo de nusinersén (BIIB058) administrado a dosis más altas en participantes con atrofia muscular espinal que han participado previamente en un estudio de investigación con nusinersén
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
Extension Study of Nusinersen (BIIB058) in Participants With Spinal Muscular Atrophy Who Previously Participated in a Study With Nusinersen
Estudio de extensión de nusinersén (BIIB058) en participantes con atrofia muscular espinal que han participado previamente en un estudio con nusinersén
A.3.2Name or abbreviated title of the trial where available
ONWARD
A.4.1Sponsor's protocol code number232SM302
A.5.4Other Identifiers
Name:INDNumber:110011
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 SponsorBiogen Idec Research Limited
B.1.3.4CountryUnited Kingdom
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 supportBiogen Idec Research Limited
B.4.2CountryUnited Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationBiogen Idec Research Limited
B.5.2Functional name of contact pointMedical Director
B.5.3 Address:
B.5.3.1Street AddressInnovation House, 70 Norden Road
B.5.3.2Town/ cityMaidenhead
B.5.3.3Post codeSL6 4AY
B.5.3.4CountryUnited Kingdom
B.5.4Telephone number+3491310 71 10
B.5.6E-mailclinicaltrials@biogen.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/3/12/976
D.3 Description of the IMP
D.3.1Product nameNusinersen
D.3.2Product code ISIS 396443, BIIB058
D.3.4Pharmaceutical form Solution for injection
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIntrathecal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNNUSINERSEN
D.3.9.1CAS number 125894-36-9
D.3.9.2Current sponsor codeISIS 396443 (BIIB058)
D.3.9.3Other descriptive nameNUSINERSEN SODIUM
D.3.9.4EV Substance CodeSUB189898
D.3.10 Strength
D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number12.0
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 Yes
D.3.11.13.1Other medicinal product type2'-O-(2-methoxyethyl) phosphorothioate antisense oligonucleotide
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
Muscular Atrophy, Spinal
Atrofia Muscular Espinal
E.1.1.1Medical condition in easily understood language
Spinal Muscular Atrophy (SMA)
Atrofia Muscular Espinal (AME)
E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 20.1
E.1.2Level PT
E.1.2Classification code 10041582
E.1.2Term Spinal muscular atrophy
E.1.2System Organ Class 10010331 - Congenital, familial and genetic 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 this study is to evaluate the long-term safety and tolerability of nusinersen administered intrathecally at higher doses to participants with spinal muscular atrophy (SMA) who previously participated in study 232SM203 (NCT04089566).
El objetivo principale de este estudio son evaluar a largo plazo la eficacia y tolerabilidad de nusinersen administrado por vía intratecal en dosis superiores a participantes con Atrofia muscular espinal (AME) que han participado previamente en el estudio 232SM203 (NCT04089566).
E.2.2Secondary objectives of the trial
The secondary objective of this study is to evaluate the long-term efficacy of nusinersen administered intrathecally at higher doses to participants with SMA who previously participated in study 232SM203 (NCT04089566).
El objetivo secundario de este estudio es evaluar a largo plazo la eficacia de nusinersen administrado por vía intratecal en dosis superiores a participantes con Atrofia muscular espinal (AME) que han participado previamente en el estudio 232SM203 (NCT04089566).
E.2.3Trial contains a sub-study No
E.3Principal inclusion criteria
- Completed the Day 302 visit in study 232SM203 (NCT04089566) in accordance with the study protocol.
-Haber completado la visita del día 302 del estudio 232SM203 ((NCT04089566) y cumplimiento con el protocolo del estudio.
E.4Principal exclusion criteria
- Treatment with another investigational therapy or enrollment in another interventional clinical study after the Day 302 visit in study 232SM203 (NCT04089566).
- Treatment with Zolgensma (all participants) after the Day 302 visit of study 232SM203 (NCT04089566). - Treatment with an approved therapy for SMA (other than Zolgensma) that is inconsistent with protocol requirements for allowed or disallowed concomitant therapies

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
- Haber recibido otro tratamiento en investigación o inscripción en otro estudio clínico intervencionista después de la visita del día 302 en el estudio 232SM203 (NCT04089566).
- Tratamiento con Zolgensma (todos los participantes) después de la visita del día 302 del estudio 232SM203 (NCT04089566).
- tratamiento aprobado para la AME (aparte de Zolgensma) que que sea incompatible con los requisitos del protocolo para las terapias concomitantes permitidas o no permitidas.

NOTA: Pueden aplicarse otros criterios de inclusión/exclusión definidos por el protocolo.
E.5 End points
E.5.1Primary end point(s)
1) Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
2) Change from Baseline in Growth Parameters
3) Number of Participants With Shifts from Baseline in Clinical Laboratory Parameters
4) Number of Participants With Shifts from Baseline in Electrocardiogram (ECG)
5) Number of Participants With Shifts from Baseline in Vital Signs
6) Change from Baseline in Activated Partial Thromboplastin Time (aPTT)
7) Change from Baseline in Prothrombin Time (PT)
8) Change from Baseline in International Normalized Ratio (INR)
9) Change from Baseline in Urine Total Protein
10) Change from Baseline in Neurological Examination Outcomes for Participants </= 2years of age
11) Change from Baseline in Neurological Examination Outcomes for Participants > 2 years of age
12) Percentage of Participants With a Postbaseline Platelet Count Below the Lower Limit of Normal on at least 2 Consecutive Measurements
13) Percentage of Participants With a Postbaseline Corrected QT Interval Using Fridericia’s Formula (QTcF) of >500 millisecond (msec) and an Increase from Baseline to Any Postbaseline Timepoint in QTcF of >60 msec
1.Número de participantes con efectos adversos AA y efectos adversos serios AAG.
2.Cambio de los parámetros de crecimiento con respecto al inicio
3.Número de participantes con cambios en los parámetros de laboratorio clínico con respecto al inicio
4.Número de participantes con cambios en el electrocardiograma (ECG) con respecto al inicio
5.Número de participantes con cambios en los signos vitales con respecto al inicio
6.Cambio en el tiempo de tromboplastina parcial activada (aPTT) con respecto al valor inicial
7.Cambio en el tiempo de protrombina (TP) con respecto al valor inicial
8.Cambio en el ratio internacional normalizado (INR) con respecto a la línea de base
9.Cambio con respecto al inicio en la proteína total en orina
10.Cambio con respecto al inicio en los resultados del examen neurológico para los participantes </= 2 años de edad
11.Cambio con respecto al inicio en los resultados del examen neurológico para los participantes de más de 2 años de edad
12.Porcentaje de participantes con un recuento de plaquetas posterior al inicio por debajo del límite inferior de la normalidad en al menos 2 mediciones consecutivas
13.Porcentaje de participantes con un intervalo QT corregido después del inicio utilizando la fórmula de Fridericia (QTcF) de >500 milisegundos (mseg) y un aumento desde el inicio hasta cualquier punto de tiempo después del inicio en QTcF de >60 mseg
E.5.1.1Timepoint(s) of evaluation of this end point
For Primary endpoints 1) , 2), 3), 4), 5), 9), 10), 11), 12), 13)
Up to Day 1081

For Primary endpoints 6), 7), 8)
Up to Day 961
Para los criterios de valoración primarios 1) , 2), 3), 4), 5), 9), 10), 11), 12), 13)

Hasta el día 1081
Para los criterios de valoración primarios 6), 7), 8)
Hasta el día 961
E.5.2Secondary end point(s)
1) Total Number of New World Health Organization (WHO) Motor Milestones
2) Number of Participants Who Used Respiratory Support, by Type
3) Number of Hours Per Day of Respiratory Support
4) Number of Days That Respiratory Support Is Used
5) Time to Death (Overall Survival)
6) Change from Baseline in Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Total Score
7) Change from Baseline in Hammersmith Infant Neurological Examination (HINE) Section 2 Motor Milestones
8) Percentage of HINE Section 2 Motor Milestone Responders
9) Percentage of Time Spent on Ventilation
10) Time to Death or Permanent Ventilation
11) Change from Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Score
12) Change from Baseline in Revised Upper Limb Module (RULM) Score
1) Número total de nuevos hitos motores de la Organización Mundial de la Salud (OMS)
2) Número de participantes que utilizaron asistencia respiratoria, por tipo
3) Número de horas diarias de asistencia respiratoria
4) Número de días en que se utiliza la asistencia respiratoria
5) Tiempo hasta la muerte (supervivencia global)
6) Cambio desde el inicio en la puntuación total de la prueba infantil de trastornos neuromusculares del Hospital Infantil de Filadelfia (CHOP INTEND)
7) Cambio con respecto al valor inicial en la sección 2 de los hitos motores del Hammersmith Infant Neurological Examination (HINE)
8) Porcentaje de respuesta a los hitos motores de la sección 2 del HINE
9) Porcentaje de tiempo de ventilación
10) Tiempo hasta la muerte o la ventilación permanente
11) Cambio desde el inicio en la puntuación de la Escala Funcional Motora de Hammersmith (HFMSE)
12) Cambio desde el inicio en la puntuación del módulo revisado de extremidades superiores (RULM)
E.5.2.1Timepoint(s) of evaluation of this end point
Up to Day 1081
Hasta el día 1081
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 No
E.6.8Bioequivalence No
E.6.9Dose response No
E.6.10Pharmacogenetic Yes
E.6.11Pharmacogenomic Yes
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) No
E.7.3Therapeutic confirmatory (Phase III) Yes
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 No
E.8.1.6Cross over No
E.8.1.7Other Yes
E.8.1.7.1Other trial design description
Asignación paralela
Parallel Assignment
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.8.3 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 concerned4
E.8.5The trial involves multiple Member States Yes
E.8.5.1Number of sites anticipated in the EEA24
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
Argentina
Australia
Brazil
Canada
Chile
Colombia
Israel
Korea, Republic of
Lebanon
Mexico
Russian Federation
Saudi Arabia
Taiwan
Turkey
United States
Estonia
France
Germany
Greece
Hungary
Ireland
Italy
Latvia
Poland
Spain
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
LVLS
UVUS
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years3
E.8.9.1In the Member State concerned months11
E.8.9.1In the Member State concerned days
E.8.9.2In all countries concerned by the trial years4
E.8.9.2In all countries concerned by the trial months11
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: 140
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: 92
F.1.1.5Children (2-11years) Yes
F.1.1.5.1Number of subjects for this age range: 45
F.1.1.6Adolescents (12-17 years) Yes
F.1.1.6.1Number of subjects for this age range: 3
F.1.2Adults (18-64 years) Yes
F.1.2.1Number of subjects for this age range: 12
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 state7
F.4.2 For a multinational trial
F.4.2.1In the EEA 52
F.4.2.2In the whole clinical trial 152
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)
Continued use after completing study requirements will be at the discretion of the participant and
Investigator through prescription or commercial sources, as available.
El uso continuado después de completar los requisitos del estudio será a discreción del participante y del
Investigador a través de la prescripción o de fuentes comerciales, según esté disponible.
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 Decision2021-05-05
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2021-03-10
P. End of Trial
P.End of Trial StatusOngoing

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