Clinical Trials Register

Summary
EudraCT Number:	2016-000778-40
Sponsor's Protocol Code Number:	BP39056
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2016-08-05
Trial results	View 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.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2016-000778-40

A.3

Full title of the trial

A TWO PART SEAMLESS, OPEN-LABEL, MULTICENTER STUDY TO INVESTIGATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS AND EFFICACY OF RO7034067 IN INFANTS WITH TYPE1 SPINAL MUSCULAR ATROPHY

ESTUDIO DE CONTINUIDAD EN DOS PARTES, ABIERTO, MULTICÉNTRICO, PARA INVESTIGAR LA SEGURIDAD, LA TOLERABILIDAD, LA FARMACOCINÉTICA, LA FARMACODINÁMICA Y LA EFICACIA DE RO7034067 EN LACTANTES CON ATROFIA MUSCULAR ESPINAL DE TIPO 1

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of RO7034067 in Infants with Type1 Spinal Muscular Atrophy

Estudio para investigar la seguridad, la tolerabilidad, la farmacocinética, la farmacodinamia y la eficacia de RO7034067 en lactantes con atrofia muscular espinal tipo 1

A.4.1

Sponsor's protocol code number

BP39056

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/080/2018

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	F. Hoffmann-La Roche Ltd
B.1.3.4	Country	Switzerland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	F. Hoffmann-La Roche Ltd
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	F.Hoffmann-La Roche Ltd
B.5.2	Functional name of contact point	Trial Information Support Line-TISL
B.5.3	Address:
B.5.3.1	Street Address	Grenzacherstrasse 124
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4070
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+34913257300
B.5.5	Fax number	+34913248195
B.5.6	E-mail	spain.start_up_unit@roche.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	RO7034067
D.3.2	Product code	RO7034067/F12
D.3.4	Pharmaceutical form	Powder for oral solution
D.3.4.1	Specific paediatric formulation	Yes
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	n/a
D.3.9.2	Current sponsor code	RO7034067/F12
D.3.9.3	Other descriptive name	RO7034067
D.3.9.4	EV Substance Code	SUB179686
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	RO7034067
D.3.2	Product code	RO7034067/F13
D.3.4	Pharmaceutical form	Powder for oral solution
D.3.4.1	Specific paediatric formulation	Yes
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	n/a
D.3.9.2	Current sponsor code	RO7034067/F13
D.3.9.3	Other descriptive name	RO7034067
D.3.9.4	EV Substance Code	SUB179686
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	60
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another 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.1.1

Medical condition(s) being investigated

Type 1 Spinal Muscular Atrophy (SMA)

Atrofia muscular espinal Tipo 1 (AME)

E.1.1.1

Medical condition in easily understood language

SMA is a muscular disease that affects child's muscular development leading to muscle weakness and progressive loss of movement. Type 1 children are usually diagnosed before 6 months of age.

AME es una enfermedad muscular que afecta al desarrollo muscular de los niños y lleva a debilidad muscular y perdida progresiva del movimiento.
Los niños tipo 1 son diagnosticados antes de 6 meses

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	PT
E.1.2	Classification code	10041582
E.1.2	Term	Spinal muscular atrophy
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

Part 1
•To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of RO7034067 in infants with Type 1 SMA and to select the dose for Part 2
Part 2
•To assess the efficacy of RO7034067 measured as the proportion of infants sitting without support after 12 months of treatment

Parte 1
•Evaluar la seguridad, la tolerabilidad, la farmacocinética y la farmacodinámica de RO7034067 en lactantes con AME de tipo 1, y seleccionar la dosis para la parte 2.
Parte 2
•Evaluar la eficacia de RO7034067 definida por la proporción de lactantes que pueden sentarse sin apoyo tras 12 meses de tratamiento

E.2.2

Secondary objectives of the trial

To assess:
•Safety and tolerability of RO7034067
•Pharmacokinetics of RO7034067
•Pharmacodynamic effects of RO7034067
•Effect on motor development milestones
•Effect on sitting without support and further motor development milestones
•Impact of treatment with RO7034067 on time to event (death, permanent ventilation)
•Change from baseline in the total raw score of the BSID-III gross motor scale
•To assess the proportion of infants:
•Who achieve a score of 40 or higher in the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND)
•Who achieve an increase of at least 4 points on their CHOP-INTEND score from baseline
•Who achieve head control
•Who achieve a reduction of at least 30 degrees in phase angle (respiratory inductance plethysmography)
•Who are alive without permanent ventilation
•Who do not require invasive or non-invasive respiratory support

Evaluar:
•Seguridad y tolerabilidad de RO7034067
•Farmacocinética de RO7034067
•Efectos farmacodinámicos de RO7034067
•Efecto en los hitos del desarrollo motor
•Efecto en la capacidad de sentarse sin apoyo y en otros hitos del desarrollo motor
• El impacto del tratamiento con RO7034067 en el tiempo transcurrido hasta el acontecimiento (muerte, ventilación permanente).
•El cambio desde el inicio en la puntuación total bruta de la escala de motricidad gruesa de las BSID-III
•Evaluar la proporción de lactantes que:
•Obtienen una puntuación de 40 o más en el Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND)
•Alcanzan un aumento de al menos 4 puntos en su puntuación del CHOP-INTEND desde el inicio en la puntuación
•Logran el control de la cabeza
•Alcanzan una reducción de al menos 30 grados en ángulo de fase (pletismografía respiratoria)
•Sobreviven sin ventilación permanente
•No necesitan soporte respiratorio invasivo o no invasivo

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Males and females aged between 28 days (1 month) of life and 210 days (7 months) (inclusive) at enrollment
- A legally authorized representative must be able to consent for the patient according to International Conference on Harmonisation and local regulations
- Gestational age of 37 to 42 weeks
- Confirmed diagnosis of 5q-autosomal recessive SMA, including:
•Genetic confirmation of homozygous deletion or compound heterozygosity predictive of loss of function of the survival motor neuron 1 (SMN1) gene
•Clinical history, signs or symptoms attributable to Type 1 SMA, i.e., hypotonia, absent deep tendon reflexes and/or tongue fasciculations with onset after the age of 28 days, but prior to the age of 3 months (inclusive), and inability to sit independently (without support) at the time of screening
- Infant has two SMN2 gene copies, as confirmed by central testing
- Body weight >= 3rd percentile for age, using appropriate country-specific guidelines (for the first infant only > 7 kg)
- Receiving adequate nutrition and hydration (with or without gastrostomy) at the time of screening, in the opinion of the Investigator
- Adequately recovered from any acute illness at the time of screening and considered well-enough to participate in the opinion of the Investigator

-Niños y niñas de entre 28 días (1 mes) y 210 días (7 meses) (inclusive) de vida en el momento de la inclusión.
-De acuerdo con las normas de la Conferencia Internacional de Armonización y la normativa local, un representante legalmente autorizado debe tener capacidad de otorgar el consentimiento por el paciente.
-Edad gestacional de entre 37 y 42 semanas.
-Diagnóstico confirmado de AME con cromosoma 5q autosómico recesivo, lo que abarca:
•Confirmación genética de deleción homocigótica o heterocigosidad compuesta predictiva de la pérdida de la función del gen SMN1.
•Historia clínica, signos o síntomas atribuibles a la AME de tipo 1, es decir, hipotonía, ausencia de reflejo tendinoso profundo (RTP) y/o fasciculaciones de la lengua que se inician después de los 28 días de vida, pero antes de la edad de 3 meses (inclusive), e incapacidad para sentarse solo (sin apoyo) en el momento de la selección.
-El paciente tiene dos copias del gen SMN2, confirmado por las pruebas centralizadas.
6) Peso corporal >=3er percentil para la edad, según las directrices específicas de cada país (solo para el primer lactante: > 7 kg).
-Nutrición e hidratación adecuadas (con o sin gastrostomía) en el momento de la selección, según la opinión del investigador.
-Recuperado adecuadamente de cualquier enfermedad aguda en el momento de la selección y considerado lo bastante sano como para participar, según la opinión del investigador.

E.4

Principal exclusion criteria

- Concomitant or previous participation in any investigational drug or device study within 90 days prior to screening or 5 half-lives, whichever is longer
- Concomitant or previous administration of a SMN2 targeting antisense oligonucleotide or SMN2 splicing modifier or gene therapy either in a clinical study or as part of medical care.
- Any history of cell therapy
- Hospitalization for pulmonary event within the last 2 months, or planned at the time of screening
- Unstable gastrointestinal, renal, hepatic, endocrine or cardiovascular system diseases
- Inadequate venous or capillary blood access for the study procedures
- Patients requiring invasive ventilation or tracheostomy
- Patients requiring awake non-invasive ventilation or with awake hypoxemia (arterial oxygen saturation < 95%) with or without ventilator support
- Patients with a history of respiratory failure or severe pneumonia, and have not fully recovered their pulmonary function at the time of screening
- Multiple or fixed contractures and/or hip subluxation or dislocation at birth
- Presence of non-SMA related concurrent syndromes or diseases
- Confirmed (2 consecutive measurements) systolic blood pressure or diastolic blood pressure outside the 95th percentile for age; resting heart rate < 70 bpm or > 170 bpm
- Presence of clinically relevant electrocardiogram (ECG) abnormalities before study drug administration
- History of malignancy if not considered cured
- Any major illness within one month before the screening examination or any febrile illness within one week prior to screening and up to first dose administration
- Taking any nutrients known to modulate cytochrome [CYP] 3A activity within 2 weeks prior to administration of study drugs
- The infant (and the mother, if breastfeeding the infant):
• Any inhibitor of CYP3A4 taken within 2 weeks (or within 5 times the elimination half life, whichever is longer) prior to dosing, including but not limited to ketoconazole, miconazole, itraconazole, fluconazole, erythromycin, clarithromycin, ranitidine, cimetidine
• Any inducer of CYP3A4 taken within 4 weeks (or within 5 times the elimination half-life, whichever is longer) prior to dosing, including but not limited to rifampicin, rifabutin, glucocorticoids, carbamazepine, phenytoin, phenobarbital, St. John's wort
• Any organic cation transporter-2 and multidrug and toxic compound extrusion substrates shall be avoided
• Any known flavin containing monooxygenase (FMO) 1 or FMO3 inhibitors or substrates
- Clinically significant abnormalities in laboratory test results
- Ascertained or presumptive hypersensitivity to RO7034067 or the constituents of its formulation
- Prior use (at any time in the patients’ lives) and/or, anticipated need for quinolones (chloroquine and hydroxychloroquine), thioridazine, hydroxychloroquine, vigabatrin, retigabine, or any other drug known to cause retinal toxicity during the study. Infants exposed to chloroquine, hydroxycholoroquine, thioridazine, vigabatrin, retigabine or drugs with known retinal toxicity given to mothers during pregnancy (and lactation) should not be enrolled.
- Recent history (less than 6 months) of ophthalmic disease that would interfere with the conduct of the study as assessed by an ophthalmologist

-Participación previa o concomitante en cualquier estudio con un fármaco o dispositivo experimental en un plazo de 90 días antes de la selección o 5 semividas, lo que sea más largo.
-Administración previa o concomitante de un oligonucleótido en antisentido dirigido contra el SMN2, modificadores del procesado del SMN2 o una terapia génica en el marco de un ensayo clínico o de la atención médica.
-Cualquier antecedente de terapia celular.
-Hospitalización a causa de un acontecimiento pulmonar en los últimos 2 meses o que esté prevista en el momento de la selección.
-Enfermedades gastrointestinales, renales, hepáticas, endocrinas o del sistema cardiovascular inestables.
-Acceso sanguíneo venoso o capilar inadecuado para los procedimientos del estudio
-Pacientes que precisen de ventilación invasiva o de una traqueotomía.
-Pacientes que precisen de ventilación no invasiva mientras están despiertos o con hipoxemia mientras están despiertos (SaO2 < 95 %) con o sin soporte ventilador.
-Pacientes con antecedentes de fallo respiratorio o neumonía grave, y que no hayan recuperado completamente la función pulmonar en el momento de la selección.
-Contracturas múltiples o fijas y/o subluxación o dislocación de la cadera al nacer.
-Presencia de síndromes o enfermedades concomitantes no relacionadas con la AME.
-Tensión arterial sistólica (TAS) o tensión arterial diastólica (TAD) confirmadas (2 mediciones consecutivas) fuera del percentil 95 para la edad; ritmo cardiaco en reposo <70 lpm o >170
-Presencia de anomalías en el electrocardiograma (ECG) significativas desde el punto de vista clínico antes de la administración del fármaco del estudio
-Antecedentes de neoplasia maligna que no se considere curada.
-Cualquier enfermedad importante un mes antes de las pruebas de la selección o cualquier enfermedad febril en el plazo de una semana antes de la selección y hasta la administración de la primera dosis.
-Pacientes que hayan tomado nutrientes conocidos por modular la actividad del CYP3A en las 2 semanas previas a la administración de los fármacos del estudio.
-El lactante (y la madre, si está en periodo de lactancia):
•Cualquier inhibidor del CYP3A4 tomado en las 2 semanas previas a la administración (o en 5 veces la semivida de eliminación, lo que sea más largo) incluidos, entre otros: ketoconazol, miconazol, itraconazol, fluconazol, eritromicina, claritromicina, ranitidina,
cimetidina
• Cualquier inhibidor del CYP3A4 tomado en las 4 semanas previas a la administración (o en 5 veces la semivida de eliminación, lo que sea más largo) incluidos, entre otros: rifampicina, rifabutina, glucocorticoides, carbamazepina, fenitoína, fenobarbital, hierba de San Juan.
• Se evitará cualquier sustrato de TCO-2 y MATE
• Cualquier inhibidor o sustrato conocido de la FMO1 o la FMO3.
-Anomalías significativas desde el punto de vista clínico en los resultados de pruebas analíticas
-Hipersensibilidad conocida o presunta a RO7034067 o a los componentes de su formulación.
-El uso previo (en cualquier momento de la vida de los pacientes) y/o la necesidad prevista de quinoloinas (cloroquina e hidroxicloroquina), tioridazina, vigabatrina, retigabina o cualquier otro fármaco con efectos conocidos por causar toxicidad retiniana durante el estudio impide la participación en este ensayo. No se debe incluir a los lactantes expuestos a cloroquina, hidroxicloroquina, tioridazina, vigabatrina, retigabina o fármacos con efectos conocidos por causar toxicidad retiniana administrados a las madres durante el embarazo (y la lactancia).
-Antecedentes recientes (menos de 6 meses) de enfermedades oftálmicas que pudieran interferir con la realización del estudio, en función de la evaluación de un oftalmólogo.

E.5 End points

E.5.1

Primary end point(s)

Part 1 and 2: Safety
1. Incidence and severity of adverse events (AE) and serious adverse events
2. Incidence of treatment discontinuations due to AE
3. Incidence of abnormal laboratory and ECG values
4. Vital signs abnormalities
5. Anthropometric and ophthalmological examination
Part 1
Pharmacokinetics
6. Plasma concentrations of RO7034067, and its metabolite(s)

Pharmacodynamic
7. Assessment of SMN protein in blood
8. Assessment of SMN messenger ribonucleic acid (mRNA) in blood
Part 2: Efficacy
9. Proportion of infants who are sitting without support at 12 months of treatment assessed by the Gross Motor Scale of the Bayley Scales of Infant and Toddler development – Third Edition (BSID-III)

Parte 1 y 2: Seguridad
1. Incidencia y severidad de los acontecimientos adversos (AE)y de los acontecimientos adversos graves.
2. Incidencia de la discontinuación de los tratamientos debido a AE
3. Incidencia de valores de laboratorio y ECG anormales
4. Anormalidades de los signos vitales
5. Exploración antropométrica y oftalmológica
Parte 1
Farmacocinética
6. Concentraciones plasmáticas de RO7034067, y su(s) metabolito(s)
Farmacodinamia
7. Evaluación de la proteína SMN en sangre
8. Evaluación del SMN acido ribonucleico mensajero (ARNm) en sangre
Parte 2: Eficacia
9. Proporción de lactantes que pueden sentarse sin apoyo tras 12 meses de tratamiento conforme la escala de motricidad gruesa de las Escalas Bayley de Desarrollo Infantil,tercera edición (BSID-III)

E.5.1.1

Timepoint(s) of evaluation of this end point

1-4. Up to 2 years
5. Screening (D [Day] -30 to D -2), D56, D119, D182, D245, D301, D364, D427, D490, D546, D609, D672, D728
6. D1, D2, D7, D14, D28, D56, D84, D119, D182, D245, D301, D364, D427, D490, D546, D609, D672, D728
7. D1, D14, D28, D119, D245, D364, D609, D728
8. D1, D14, D28, D245, D364, D609, D728
9. At Month 12

1-4. Hasta un máximo de 2 años
5. Screening (D [Dia -30 a D -2), D56, D119, D182, D245, D301, D364, D427, D490, D546, D609, D672, D728
6. D1, D2, D7, D14, D28, D56, D84, D119, D182, D245, D301, D364, D427, D490, D546, D609, D672, D728
7. D1, D14, D28, D119, D245, D364, D609, D728
8. D1, D14, D28, D245, D364, D609, D728
9. En el mes 12

E.5.2

Secondary end point(s)

Part 2
1. Plasma concentrations of RO7034067 and its metabolite (s)
2. Assessment of SMN protein in blood
3. Assessment of SMN mRNA in blood
4. Change from baseline in the Total Raw Score of the BSID-III gross motor scale at Month 12 and 24
5. Proportion of infants who achieve the attainment levels of the motor milestones assessed in the Hammersmith Infant Neurological Examination Module 2 (HINE-2) at Month 12 and 24
6. Proportion of infants who achieve a score of 40 or higher in the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) at Month 12
7. Proportion of infants who achieve an increase of at least 4 points in their CHOP-INTEND score from baseline at Month 8 and Month 12
8. Proportion of infants who achieve head control at Month 8, Month 12, and Month 24
9. Proportion of infants who achieve a reduction of at least 30 degrees in their phase angle from baseline, as measured by respiratory inductance plethysmography, at Month 12
10. Time to permanent ventilation (from enrollment)
11. Proportion of infants who are alive at Month 12 and 24
12. Proportion of infants who are alive without permanent ventilation at Month 12 and 24
13. Proportion of infants who do not require invasive or non-invasive respiratory support at Month 12 and Month 24
14. Ability to swallow and to feed orally at Month 12 and Month 24

Parte 2
1. Concentraciones plasmáticas de RO7034067 y su(s) metabolito(s)
2. Evaluación de la proteína SMN en sangre
3. Evaluación del SMN ARNm en sangre
4. Investigar el cambio desde el inicio en la puntuación total bruta de la escala de motricidad gruesa de las BSID-III en el mes 12 y en el mes 24 de tratamiento.
5. Proporcion de lactantes que alcanzan la consecución de hitos del desarrollo motor a los 12 y 24 meses conforme el módulo 2 del Examen neurológico infantil de Hammersmith (HINE).
6. Proporción de lactantes que obtienen una puntuación de 40 o más en el Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) a los 12 meses de tratamiento.
7. Proporción de lactantes que alcanzan un aumento de al menos 4 puntos en su puntuación del CHOP-INTEND desde el inicio en la puntuación a los 8 y 12 meses de tratamiento.
8. Proporción de lactantes que logran el control de la cabeza a los 8, 12 y 24 meses de tratamiento
9. Proporción de lactantes que alcanzan una reducción de al menos 30 grados en ángulo de fase a los 12 meses de tratamiento medida mediante pletismografía respiratoria.
10. Tiempo a ventilación permanente (desde inclusión)
11. Proporcion de lactantes que están vivos a los 12 y 24 meses
12. Proporción de lactantes que están vivos sin ventilacion permanente a los 12 y 24 meses.
13. Proporción de lactantes que no necesitan soporte respiratorio invasivo o no invasivo a los 12 y 24 meses de tratamiento.
14. Habilidad para tragar y alimentarse oralmente en los meses 12 y 24

E.5.2.1

Timepoint(s) of evaluation of this end point

1. D1, D2, D14, D28, D56, D119, D182, D245, D301, D364, D427, D490, D546, D609, D672, D728
2. D1, D28, D119, D245, D364, D609, D728
3. D1, D28, D245, D364, D609, D728
4. Baseline, Month 12 and 24
5. Month 12 and 24
6. Month 12
7. Month 8 and 12
8. Month 8, Month 12 and 24
9. Baseline and Month 12
10. Up to 2 years
11-14. At Month 12 and 24

1. D1, D2, D14, D28, D56, D119, D182, D245, D301, D364, D427, D490, D546, D609, D672, D728
2. D1, D28, D119, D245, D364, D609, D728
3. D1, D28, D245, D364, D609, D728
4. Basal, Meses 12 y 24
5. Meses 12 y 24
6. Mes 12
7. Meses 8 y 12
8. Mes 8, Mes 12 y Mes 24
9. Basal y Mes 12
10. Hasta un máximo de 2 años
11-14. En el Mes 12 y 24

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

genetic testing

Análisis genético

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Diseño en 2 partes

2 part design

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Belgium

Brazil

Canada

China

Croatia

France

Germany

Italy

Japan

Lebanon

Poland

Russian Federation

Saudi Arabia

Serbia

Spain

Switzerland

Turkey

Ukraine

United Kingdom

United States

E.8.7

Trial 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

The end of this study is defined as the date when the last patient last visit (LPLV) occurs.
The study will continue until RO7034067 is commercially available in the infant’s country, or as per local regulation, or per the Sponsor’s decision to terminate RO7034067 development. However, the study will not exceed 4 years (or less as per country specific requirements) after the last infant is enrolled in the study.

El final de este estudio se define como la fecha en que tenga lugar la última visita del último paciente (UVUP)
El estudio continuará hasta que RO7034067 se comercialice en el país del lactante, o según la normativa local, o si el promotor decide finalizar el desarrollo de RO7034067. No obstante, el estudio no excederá los 4 años (o menos, según los requisitos específicos de cada país) después de la inclusión del último lactante en el estudio.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

Yes

F.1.1.4.1

Number of subjects for this age range:

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

informed consent for study participation will be obtained from parents or legal guardian

El consentimiento informado para la participación en el estudio se obtendrá de los padres o tutores legales

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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)

Post-trial access to study drug (SD) to eligible patients is offered free of charge according to the Roche Global Policy. A patient will be eligible to receive SD after the end of study if all of these conditions are met:patient has a life-threatening or severe medical condition and requires continued SD treatment for his or her well-being/no appropriate alternative treatments available/patient and his or her doctor comply with and satisfy any legal or regulatory requirements that apply to them

El acceso post-estudio al fármaco del ensayo (FE) en pacientes elegibles se ofrecerá gratis segun política global de Roche. Un paciente será elegible para recibir el FE después del final del estudio si todas estas condiciones se cumplen: El paciente tiene una enfermedad severa o amenazante para la vida que requiere tratamiento continuado con el FE para su bienestar/no hay tratamientos alternativos previos/paciente y su medico cumplen cualquier requerimiento legal o regulatorio que les aplique

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2018-08-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-07-19

P. End of Trial
P.	End of Trial Status	Prematurely Ended

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials