Clinical Trials Register

Summary
EudraCT Number:	2016-000750-35
Sponsor's Protocol Code Number:	BP39055
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2016-06-28
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

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2016-000750-35

A.3

Full title of the trial

A TWO-PART SEAMLESS, MULTI-CENTER RANDOMIZED, PLACEBO-CONTROLLED, DOUBLE BLIND STUDY TO INVESTIGATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS AND EFFICACY OF RO7034067 IN TYPE 2 AND 3 SPINAL MUSCULAR ATROPHY PATIENTS.

UNO STUDIO IN DUE PARTI IN CONTINUO, IN DOPPIO CIECO, CONTROLLATO CON PLACEBO, RANDOMIZZATO MULTICENTRICO PER VALUTARE LA SICUREZZA, TOLLERABILITÀ, FARMACOCINETICA, FARMACODINAMICA ED EFFICACIA DI RO7034067 IN PAZIENTI CON ATROFIA MUSCOLARE SPINALE DI TIPO 2 E 3

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 Type 2 and 3 Spinal Muscular Atrophy Patients

Uno studio per valutare sicurezza, tollerabilità, farmacocinetica, farmacodinamica ed efficacia di RO7034067 in pazienti con atrofia muscolare spinale di tipo 2 e 3.

A.4.1

Sponsor's protocol code number

BP39055

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

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.5.6	E-mail	global.rochegenentechtrials@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/F06 with solvent (RO7034067/F08)
D.3.4	Pharmaceutical form	Powder and solvent 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/F06
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/F07 with solvent (RO7034067/F09)
D.3.4	Pharmaceutical form	Powder and solvent 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/F07
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	120
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Powder and solvent for oral solution
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Powder and solvent for oral solution
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Spinal Muscular Atrophy (SMA)

Atrofia Muscolare Spinale (SMA)

E.1.1.1

Medical condition in easily understood language

Spinal Muscular Atrophy, a genetic progressive neuromuscular disease characterized by profound weakness and muscle atrophy that is the leading genetic cause of death in babies and toddlers.

Atrofia Muscolare Spinale, una malattia genetica neuromuscolare progressiva caratterizzata da una profonda debolezza ed atrofia muscolare cause genetiche principali di decesso in bambini e adolescenti

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	19.0
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 (PK) and Pharmacodynamics (PD) of RO7034067 in patients with Type 2 and Type 3 (ambulant or non-ambulant) SMA, and to select the dose for Part 2 of the study

Part 2:
•To evaluate efficacy of RO7034067 compared to placebo in terms of motor function in Type 2 and non-ambulant Type 3 SMA patients, as assessed by the change from baseline in the total score of the Motor Function Measure (MFM) at 12 months

Parte 1
•Valutare sicurezza, tollerabilità, farmacocinetica e farmacodinamica di RO7034067 in pazienti affetti da SMA di tipo 2 e di tipo 3 (deambulanti o non deambulanti) e selezionare la dose per la Parte 2 dello studio.
Parte 2
•Valutare l'efficacia di RO7034067 rispetto al placebo in termini di funzione motoria in pazienti affetti da SMA di tipo 2 e non deambulanti affetti dalla malattia di tipo 3, determinandola in base alla variazione rispetto al basale nel punteggio totale della
misura della funzione motoria (MFM) a 12 mesi

E.2.2

Secondary objectives of the trial

Part 2:
•To investigate the PK/PD relationship of RO7034067 by PK/PD modeling
•To investigate the efficacy of 12 month treatment with RO7034067 in terms of motor function as assessed by the Hammersmith Functional Motor Scale Expanded (HFMSE), the revised upper limb module (RULM) and responder analyses of the MFM
•To investigate the efficacy of 12 month treatment with RO7034067 in terms of respiratory function as assessed by Sniff nasal inspiratory pressure (SNIP) and, in patients aged 6 years and older,by Forced vital capacity (FVC),Forced expiratory volume (FEV1) and Peak cough flow (PCF)
•To investigate the proportion of patients who experience a pre-specified disease related adverse event by Month 12
•To investigate the effect of RO7034067 on patient-reported quality of life at Month 12,as assessed by the Pediatric Quality of Life Inventory (PedsQL) 3.0 Neuromuscular module and the PedsQL 4.0 Generic Core Scale
•To investigate the safety and tolerability of RO7034067 treatment

Esaminare la correlazione PK/PD di RO7034067 mediante un modello di PK/PD
•Esaminare l'efficacia del trattamento di 12 mesi con RO7034067 in termini di funzione motoria valutata utilizzando la scala funzionale HFMSE, il test RULM e le analisi della MFM nei soggetti responsivi.
•Esaminare l'efficacia del trattamento di 12 mesi con RO7034067 in termini di funzione respiratoria valutata utilizzando la pressione inspiratoria nasale tramite test SNIP e, nei pazienti di età pari a superiore a 6 anni, la capacità vitale forzata (FVC), il volume espiratorio forzato FEV1 e il picco di flusso della tosse (PCF).
•Esaminare la percentuale di pazienti che manifestano un evento avverso pre specificato, correlato alla malattia, entro il mese 12.
•Esaminare l'effetto di RO7034067 sulla qualità della vita riferita dai pazienti al mese 12, valutata utilizzando il questionario PedsQL 3.0 e la scala generica PedsQL 4.0.
•Esaminare la sicurezza e la tollerabilità del trattamento con RO7034067

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Males and females 2 to 25 years of age inclusive
- For Part 1: Type 2 or 3 SMA ambulant or non-ambulant. For Part 2: Type 2 or 3 SMA non-ambulant.
Non-ambulant is defined as not having the ability to walk unassisted for 10 m or more
- Confirmed diagnosis of 5q-autosomal recessive SMA
- Negative blood pregnancy test at screening and agreement to comply with measures to prevent pregnancy and restrictions on sperm donation

Soggetti di sesso maschile e femminile di età da 2 a 25 anni compresi.
- Per la Parte 1: SMA di tipo 2 o 3, deambulanti o non deambulanti.
- Per la Parte 2: SMA di tipo 2 o 3 non deambulanti. Con non deambulante si intende non in grado di camminare senza assistenza per almeno 10 metri o più.
- Diagnosi confermata di SMA autosomica recessiva 5q.
- Test di gravidanza sul sangue negativo al momento dello screening e accettazione del rispetto delle misure di prevenzione della gravidanza e delle limitazioni della donazione di sperma

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 of the drug, whichever is longer
- Concomitant or previous participation at any time in a Survival of motor neuron (SMN)-2 targeting antisense oligonucleotide, SMN2 splicing modifier or gene therapy study
- Any history of cell therapy
- Hospitalization for a pulmonary event within the last 2 months or planned at time of screening
- Surgery for scoliosis or hip fixation in the one year preceding screening or planned within the next 18 months
- Unstable gastrointestinal, renal, hepatic, endocrine, or cardiovascular system diseases as considered to be clinically significant by the Investigator
- Presence of clinically significant ECG abnormalities before study drug administration from average of triplicate measurement or cardiovascular disease indicating a safety risk for patients as determined by the Investigator
- History of malignancy if not considered cured
- Significant risk for suicidal behavior, in the opinion of the Investigator as assessed by the C-SSRS (>6 years of age)
- 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 P450 (CYP) 3A activity (e.g., grapefruit juice; Seville orange) within 2 weeks prior to administration of study drugs
- 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 (OCT)-2 and multidrug and toxin extrusion (MATE) substrates within 2 weeks before dosing
- Use of the following medications within 90 days prior to randomization: riluzole, valproic acid, hydroxyurea, sodium phenylbutyrate, butyrate derivatives, creatine, carnitine, growth hormone, anabolic steroids, probenecid, agents anticipated to increase or decrease muscle strength, agents with known or presumed histone deacetylase (HDAC) inhibitory effect, and medications with known phototoxicity liabilities
- Recently initiated treatment (within < 6 months prior to randomization) with oral salbutamol or another 2-adrenergic agonist taken orally
- Any prior use of chloroquine, hydroxychloroquine, retigabin, vigabatrin or thioridazine, is not allowed.
- Clinically significant abnormalities in laboratory test results
- Donation or loss of blood >= 10% of blood volume within three months prior to screening
- Ascertained or presumptive hypersensitivity (e.g., anaphylactic reaction) to RO7034067 or to the constituents of its formulation
- Recent history (less than one year) of ophthalmological diseases

Partecipazione concomitante o precedente a qualsiasi studio su un farmaco o un dispositivo sperimentale nei 90 giorni precedenti allo screening o nelle 5 emivite del farmaco, a seconda di quale dei due sia il periodo più lungo.
- Partecipazione concomitante o precedente in qualsiasi momento a uno studio su un oligonucleotide antisenso mirato a SMN (Survival of Motor Neuron)-2, su un modificatore dello splicing di SMN2 o su una terapia genica.
- Qualsiasi anamnesi di terapia cellulare.
- Ricovero ospedaliero per un evento polmonare negli ultimi 2 mesi o pianificato al momento dello screening.
- Intervento chirurgico per la scoliosi o la riparazione dell'anca nell'anno precedente allo screening o pianificato nei prossimi 18
mesi.
- Malattie gastrointestinali, renali, epatiche, endocrine o cardiovascolari instabili, considerate clinicamente significative dallo
sperimentatore.
- Presenza di anomalie clinicamente significative sull'ECG prima della somministrazione del farmaco dello studio da una media di
misurazioni in triplicato o malattia cardiovascolare, a indicare un rischio per la sicurezza dei pazienti come determinato dallo
sperimentatore.
- Anamnesi di neoplasia se non considerata curata.
- Rischio significativo di comportamento suicida secondo il parere dello sperimentatore, valutato utilizzando il questionario C-SSRS
(>6 anni di età).
- Qualsiasi malattia importante nel mese precedente all'esame di screening o qualsiasi malattia febbrile nella settimana
precedente allo screening e fino alla somministrazione della prima dose.
- Assunzione di nutrienti noti per modulare l'attività del Citocromo P450 (CYP) 3A (per es. succo di pompelmo, arance amare) nelle
2 settimane precedenti alla somministrazione dei farmaci dello studio.
- Qualsiasi inibitore del CYP3A4 assunto nelle 2 settimane (o entro volte 5 l’emivita di eliminazione, a seconda di quale sia il
periodo più lungo) precedenti alla somministrazione, inclusi tra gli altri: ketoconazolo, miconazolo, itraconazolo, fluconazolo, eritromicina, claritromicina, ranitidina, cimetidina.
- Qualsiasi induttore del CYP3A4 assunto nelle 4 settimane (o entro le 5 volte dell’emivita di eliminazione, a seconda di quale sia il
periodo più lungo) precedenti alla somministrazione, inclusi tra gli altri: rifampicina, rifabutina, glucocorticoidi, carbamazepina, fenitoina, fenobarbital, iperico.
- Qualsiasi substrato di OCT-2 e MATE nelle 2 settimane precedenti alla somministrazione
- Uso dei seguenti farmaci nei 90 giorni precedenti alla randomizzazione: riluzolo, acido valproico, idrossiurea, fenilbutirrato di sodio, derivati del butirrato, creatina, carnitina, ormone della crescita, steroidi anabolizzanti, probenecid, agenti che si prevede
aumentino o riducano la forza muscolare, agenti con effetto inibitorio noto o presunto dell'istone deacetilasi (HDAC) e farmaci con effetti noti di fototossicità
- Il trattamento iniziato recentemente (entro <6 mesi prima della randomizzazione) con salbutamolo orale o un altro agonista β2-adrenergico assunto per via orale.
- Non è ammesso qualsiasi uso precedente di clorochina, idrossiclorochina, retigabin, vigabatrin o tioridazina.
- Anomalie clinicamente significative nei risultati delle analisi di laboratorio.
- Donazione o perdita di sangue ≥10% del volume ematico nei tre mesi precedenti allo screening.
- Ipersensibilità accertata o presunta (per es. reazione anafilattica) a RO7034067 o ai componenti della sua formulazione.
- Anamnesi recente (meno di un anno) di malattie oftalmologiche.

E.5 End points

E.5.1

Primary end point(s)

Part 1
1. Incidence of adverse events and serious adverse events
2. Maximum plasma concentration (Cmax) of RO7034067
3. Area under the curve (AUC) of RO7034067
4. Concentration at the end of a dosing interval (Ctrough) of RO7034067

Part 2
5. Change from baseline in the total MFM 32 score at Month 12

Parte 1
1. Incidenza di eventi avversi ed eventi avversi seri.
2. Concentrazione plasmatica massima (Cmax) di RO7034067.
3. Area sotto la curva (AUC) di RO7034067.
4. Concentrazione di RO7034067 alla fine di un intervallo di somministrazione (Ctrough).
Parte 2
5. Variazione del punteggio MFM 32 al mese 12 rispetto al basale.

E.5.1.1

Timepoint(s) of evaluation of this end point

1. Up to 24 months
2-4. Days 1, 7, 14, 28, 56, 120, 246, 365, 490, 609, and 729
5. Baseline (Day -1) and Month 12

1. Fino a 24 mesi.
2-4. Giorni 1, 7, 14, 28, 56, 120, 246, 365, 490, 609 e 729.
5. Basale (Giorno -1) e Mese 12.

E.5.2

Secondary end point(s)

Part 2
1. SMN2 mRNA in blood
2. SMN protein levels in blood
3. Change from baseline in total score of HFMSE at Month 12
4. Change from baseline in the total score of the revised upper limb module (RULM) at Month 12
5. Proportion of patients who achieve stabilization or improvement (i.e., a change from baseline >= 0) on the total MFM score at Month 12
6. Change from baseline in the MFM domain scores of D1, D2, D3 and the total combined score of (D1 + D2) at Month 12.
7. Change from baseline in the best SNIP (expressed as a percentage of the predicted value) at Month 12.
8. Change from baseline in FEV1 in patients aged 6 to 25 years at Month 12
9. Change from baseline in FVC in patients aged 6 to 25 years at Month 12.
10. Change from baseline in the peak cough flow (PCF) in patients aged 6 to 25 years at Month 12.
11. Change from baseline in the patient (aged 8-18 years only) self-reported “About my Neuromuscular Disease” domain score of the PedsQL 3.0 Neuromuscular module at Month 12
12. Change from baseline in the patient (aged 8-18 years only) self-reported Total score of the PedsQL 4.0 Generic Core Scale at Month 12
13. Proportion of patients who experience at least one disease related adverse event by Month 12

Parte 2
1. mRNA di SMN2 nel sangue.
2. Livelli della proteina SMN nel sangue.
3. Variazione nel punteggio totale HFMSE al mese 12 rispetto al basale.
4. Variazione nel punteggio totale RULM (Revised Upper Limb Module) al mese 12 rispetto al basale.
5. Quota di pazienti che hanno raggiunto una stabilizzazione od un miglioramento (per es., una variazione >=0 rispetto al basale)
del punteggio totale MFM al mese 12.
6. Variazione nei punteggi totali dei domini di MFM D1, D2, D3 ed il punteggio combinato totale (D1+D2) al mese 12.
7. Variazione dello SNIP migliore (espresso come percentuale del valore predetto) al mese 12 rispetto al basale.
8. Variazione di FEV1 al mese 12 rispetto al basale in pazienti dai 6 ai 25 anni.
9. Variazione di FVC al mese 12 rispetto al basale in pazienti dai 6 ai 25 anni.
10. Variazione di PCF (Peak Cough Flow) al mese 12 rispetto al basale in pazienti dai 6 ai 25 anni.
11. Variazione nel punteggio auto-riferito dal paziente per il dominio “La mia malattia neuromuscolare” del modulo
neuromuscolare del PedsQL 3.0 al mese 12 rispetto al basale (solo in pazienti di 8-18 anni di età).
12. Variazione nel punteggio auto-riferito dal paziente per il dominio “La mia malattia neuromuscolare” della scala generica del
PedsQL 4.0 al mese 12 rispetto al basale (solo in pazienti di 8-18 anni di età).
13. Quota di pazienti che hanno sviluppato almeno un evento avverso correlato alla malattia entro il mese 12.

E.5.2.1

Timepoint(s) of evaluation of this end point

1. Part 1: Days -1, 1, 7, 14, 28, 120, 246, 365, 729; Part 2: Days -1, 1, 7, 28, 120, 246, 365, 729
2. Part 1: Days -1, 7, 14, 28, 120, 246, 365, 729; Part 2: Days -1, 7, 28, 120, 246, 365, 729
3-12. Baseline (Day-1) and Month 12
13. Up to Month 12

. Parte 1: Giorni -1, 1, 7, 14, 28, 120, 246, 365, 729; Parte 2: Giorni -1, 1, 7,
28, 120, 246, 365, 729.
2. Parte 1: Giorni -1, 7, 14, 28, 120, 246, 365, 729; Parte 2: Giorni -1, 7, 28, 120, 246, 365, 729.
3-12. Basale (Girno-1) e mese 12.
13. Fino al mese 12.

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

Analisi genetica

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Disegno in 2 parti

2 part design

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

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

Australia

Belgium

Canada

France

Germany

Italy

Netherlands

Spain

Sweden

Switzerland

Turkey

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

Since this study includes an OLE phase for all enrolled patients, it will continue until RO7034067 is commercially available in the patient’s country, or as per local regulation, or per the Sponsor’s decision to terminate RO7034067 development. In any case the study will not exceed 4 years (or less as per country specific requirements) after the last patient is enrolled in the study.
The end of this study is defined as the date when the last patient last visit (LPLV) occurs.

Poichè lo studio comprende una fase in aperto per tutti i pazienti arruolati, proseguirà fino a che RO7034067 non sarà disponibile in commercio o in accordo alla normativa locale, o in seguito a decisione dello Sponsor di terminare lo sviluppo di RO7034067. In ogni caso lo studio non durerà più di 4 anni dopo che l’ultimo paziente è stato arruolato nello studio. La fine dello studio è definita come la data in cui si esegue l’ultima visita dell’ultimo paziente

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:

147

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)

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

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

Yes

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

Pediatric patients may provide according to local regulation informed assent
informed consent for study participation will be obtained from parents or legal guardian

pazienti pediatrici possono esprimere un assenso informato in base a quanto previsto dalla normativa locale. Il consenso informato per la partecipazione allo studio sarà ottenuto dai genitori o tutori legali

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

111

F.4.2.2

In the whole clinical trial

186

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)

A patient will be eligible to receive study drug after completing the study if all of the following conditions are met: The patient has a life-threatening or severe medical condition and requires continued study drug treatment for his or her well-being/There are no appropriate alternative treatments available to the patient/The patient and his/her doctor comply with and satisfy any legal or regulatory requirements that apply to them. See furher details in section 4.4.4 of the protocol.

Un paziente sarà idoneo a ricevere il farmaco in studio dopo la conclusione dello studio se saranno soddisfatte le seguenti condizioni: si trova in una condizione medica a rischio di vita o grave e richiede un trattamento continuo con il farmaco dello studio per il proprio benessere/non sono disponibili alternative terapeutiche appropriate per il paziente/Il paziente ed il suo medico rispettano e soddisfano i requisiti legali o regolatori che si applicano a loro. Sezione 4.4.4 del protocollo

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

2016-08-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-06-23

P. End of Trial
P.	End of Trial Status	Ongoing

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