Clinical Trials Register

Summary
EudraCT Number:	2017-004305-40
Sponsor's Protocol Code Number:	CT-AMT-061-02
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-01-20
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

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2017-004305-40

A.3

Full title of the trial

Phase III, open-label, single-dose, multi-center multinational trial investigating a serotype 5 adeno-associated viral vector containing the Padua variant of a codon-optimized human factor IX gene (AAV5-hFIXco-Padua, AMT-061) administered to adult subjects with severe or moderately severe hemophilia B

Sperimentazione multinazionale di fase III, in aperto, a dose singola, multicentrica per l’indagine su un vettore virale adeno-associato del sierotipo 5 contenente la variante Padua di un gene del fattore IX umano ottimizzato da codone (AAV5-hFIXco-Padua, AMT-061) somministrato a soggetti adulti affetti da emofilia B grave o moderatamente grave

A.3.1

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

A phase III trial investigating a gene therapy (AAV-hFIXco-Padua, AMT-061), in adult patients with severe or moderately severe haemophilia B, to firstly evaluate if it's effective, and secondly further describe it's safety profile.

Uno studio di fase III che va a studiare una terapia genica (AAV-hFIXco-Padua, AMT-061), in pazienti adulti con emofilia B grave o moderatamente grave, per valutare se è efficace e, in secondo luogo, se è sicura.

A.3.2

Name or abbreviated title of the trial where available

Phase III trial of AMT-061 in subjects with severe or moderately severe hemophilia B.

Studio di fase III di AMT-601 in pazienti con emofilia B grave o moderatamente grave

A.4.1

Sponsor's protocol code number

CT-AMT-061-02

A.5.4

Other Identifiers

Name:

IND

Number:

016248

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	UNIQURE BIOPHARMA B.V.
B.1.3.4	Country	Netherlands
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	uniQure biopharma B.V.
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	uniQure biopharma B.V.
B.5.2	Functional name of contact point	Regulatory Affairs
B.5.3	Address:
B.5.3.1	Street Address	Paasheuvelweg 25a
B.5.3.2	Town/ city	Amsterdam
B.5.3.3	Post code	1105 BP
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	00310202406000
B.5.5	Fax number	00000000000000
B.5.6	E-mail	e.destree@uniqure.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	Yes
D.2.5.1	Orphan drug designation number	EU/3/18/1999
D.3 Description of the IMP
D.3.1	Product name	AAV5-hFIXco-Padua
D.3.2	Product code	[AMT-061]
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	etranacogene dezaparvovec
D.3.9.2	Current sponsor code	AMT-061
D.3.10	Strength
D.3.10.1	Concentration unit	IU/ml international unit(s)/millilitre
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	100000000
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
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)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	Yes
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	Yes
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

Hemophilia B

Emofilia B

E.1.1.1

Medical condition in easily understood language

Hemophilia B - Bleeding disorder

Emofilia B - Disordini del sanguinamento

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10018939
E.1.2	Term	Haemophilia B (Factor IX)
E.1.2	System Organ Class	100000004850

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

The primary objective is to demonstrate the effect of AMT-061 on endogenous FIX activity 6 months after a single AMT-061 treatment.

Dimostrare l’effetto di AMT-061 sull’attività del fattore IX (FIX) endogeno 6 mesi dopo un trattamento singolo con AMT-061.

E.2.2

Secondary objectives of the trial

1. Demonstrate non-inferiority of AMT-061 as compared to standard of care continuous routine (CR) FIX prophylaxis in terms of bleeding prevention
Investigating effect of 2 x 10^13 gc/kg AMT-061 on
- Bleeding prevention
- Trough FIX activity
- Discontinuation of previous CR prophylaxis
- Consumption of FIX replacement therapy
- Occurrence & resolution of target joints
- Correlation of FIX activity levels after dosing & pre-IMP anti-AAV5 antibody titers
- Endogenous FIX activity 52 weeks after dosing.
- Exploratory efficacy objectives
2. Demonstrate additional efficacy and safety aspects of systemic administration of AMT-061.
- monitoring of AEs
- formation of anti-AAV5 antibodies (total IgM & IgG neutralizing antibodies)
- AAV5 capsid-specific T cell response
- anti-FIX antibodies
- FIX inhibitors
- hematology & serum chemistry
- shedding of vector DNA (blood & semen)
- inflammatory markers
- AST/ALT increase (corticosteroids use required to preserve FIX activity)

1.Dimostrare la non inferiorità di AMT-061 rispetto alla profilassi continua di routine con fattore IX prevista dallo standard di cura in termini di prevenzione dei sanguinamenti
Dimostrare effetti di 2 x 10^13 gc/kg AMT-061 su
- Prevenzione sanguinamento
- Attraverso attività FIX
- Interruzione precedente profilassi CR
- Consumo di terapia di rimpiazzo FIX
- Occorrenza e risoluzione di articolazioni target
- Correlazione dei livelli di attività FOX post dosaggio e pre titolo di IMP
- Attività FIX endogeno 52 settimane dopo dosaggio
- Obiettivi esploratori di efficacia
2. Dimostrare efficacia addizionale e aspetti di sicurezza di somministrazione sistemica di AMT-061
- Monitoraggio di AEs
- formazione di anticorpi anti-AAV5 (anticorpi totali neutralizzanti IgM & IgG totali)
- risposta cellule T AAV5 capside specifica
- anticorpi anti-FIX
- inibitori FIX
- ematologia e chimica clinica
- perdita di vettore DNA (sangue e seme)
- marker infiammatori
- aumento di AST/ALT

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Other types of substudies
Specify title, date and version of each substudy with relative objectives: 1. Patient Reported Outcomes, Burdens, and Experiences (PROBE) Questionnaire (optional):
- PROBE Questionnaire is a novel, patient-developed, patient-reported outcome tool specific to hemophilia and intended to capture clinical outcomes that are considered relevant by patients.
- The objective of this sub-study is to provide data complementary to the compendium of established PRO tools regarding the impact of gene therapy on patient relevant outcomes and quality of life over time.
2. Musculoskeletal Ultrasound (optional)
- This sub-study will provide objective assessment of the effects of receiving gene therapy on the progression of physiological joint damage over time.
- 8 Musculoskeletal ultrasounds to take place starting at screening. Additional ultrasounds may be collected at the investigator's discretion.

Altre tipologie di sottostudi
specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: 1-. Outcome RIportati dal Paziente, Oneri e Esperienze (PROBE) Questionario (opzionale)
- Il Questionario PROBE è un nuovo, sviluppato dal paziente, questionario per l'outcome riportato dal paziente specifico per l'emofilia e inteso a raccogliere gli outcome clinici che sono considerati rilevanti dai pazienti.
- L'obiettivo di questo sottostudio è di fornire dati complementari al compendio di strumenti PRO stabiliti a riguardo dell'impatto della terapia genica su outcome rilevanti del paziente sulla qualità della vita.
2. Ecografie Muscoloscheletrici (opzionale)
- Questo sottostudio darà valutazione degli effetti di ricevere terapia genica sulla progressione di danno articolare fisiologico.
- 8 ecografie muscoloscheletriche da effettuare a partire dallo screening. Ultrasuoni addizionali possono essere raccolti a discrezione dello sperimentatore.i

E.3

Principal inclusion criteria

- Male
- Age =18 years
- Subjects with congenital hemophilia B with known severe or moderately severe FIX deficiency (=2% of normal circulating FIX) for which the subject is on continuous routine Factor IX prophylaxis (continuous routine prophylaxis is defined as the intent of treating with an a priori defined frequency of infusions [e.g., twice weekly, once every two weeks, etc.] as documented in the medical records).
- >150 previous exposure days of treatment with FIX protein
- Have been on stable prophylaxis for at least 2 months prior to screening
- Have demonstrated capability to independently, accurately and in a timely manner complete the diary during the lead-in phase as judged by the investigator
- Acceptance to use a condom during sexual intercourse in the period from IMP administration until AAV5 has been cleared from semen, as evidenced by the central laboratory from negative analysis results for at least three consecutively collected semen samples (this criterion is applicable also for subjects who are surgically sterilized)
- Able to provide informed consent following receipt of verbal and written information about the trial.

1. Soggetti di sesso maschile
2. Età =18 anni
3. Soggetti affetti da emofilia B congenita con deficit noto di FIX grave o moderatamente grave (=2% di FIX normale circolante) per il quale il soggetto sia sottoposto a profilassi continua di routine con fattore IX*
4. >150 giorni di precedente esposizione al trattamento con la proteina FIX
5. Assunzione stabile della profilassi per almeno 2 mesi prima dello screening
6. Capacità dimostrata di compilare il diario in maniera autonoma, accurata e tempestiva durante la fase di lead-in secondo il giudizio dello sperimentatore
7. Consenso all’uso del preservativo durante i rapporti sessuali nel periodo compreso tra la somministrazione dell’IMP e l’eliminazione di AAV5 dal liquido seminale, come evidenziato dal laboratorio centrale in base all’analisi risultata negativa in almeno tre campioni di liquido seminale raccolti in sequenza (questo criterio vale anche per i soggetti resi sterili chirurgicamente)
8. Capacità di fornire il consenso informato dopo aver ricevuto informazioni verbali e scritte sulla sperimentazione.

E.4

Principal exclusion criteria

- History of factor IX inhibitors
- Positive factor IX inhibitor test at screening and Visit L-Final (based on
local laboratory results)
- Screening and Visit L-Final laboratory values (based on central
laboratory results):
a. ALT >2 times upper normal limit
b. Aspartate aminotransferase (AST) >2 times upper normal limit
c. Total bilirubin >2 times upper normal limit (except if this is caused by
Gilbert disease)
d. Alkaline phosphatase (ALP) >2 times upper normal limit
e. Creatinine >2 times upper normal limit
- Positive human immunodeficiency virus (HIV) serological test at
screening and Visit LFinal, not controlled with anti-viral therapy as
shown by CD4+ counts = 200/µL (based on central laboratory results)
- Hepatitis B or C infection with the following criteria present at screening:
I. Currently receiving antiviral therapy for this/these infection(s)
and/or
ii. Positive for any of the following (based on central laboratory results):
• Hepatitis B surface antigen (HBsAg), except if in the opinion of the
investigator this is due to a previous Hepatitis B vaccination rather than
active Hepatitis B infection
• Hepatitis B virus deoxyribonucleic acid (HBV DNA)
• Hepatitis C virus ribonucleic acid (HCV RNA)
- Known coagulation disorder other than hemophilia B
- Thrombocytopenia, defined as a platelet count below 50 × 109/L, at
screening and Visit L-Final (based on central laboratory results)
- Known severe infection or any other significant concurrent,
uncontrolled medical condition including, but not limited to, renal,
hepatic, cardiovascular, hematological, gastrointestinal, endocrine,
pulmonary, neurological, cerebral or psychiatric disease, alcoholism,
drug dependency or any other psychological disorder evaluated by the
investigator to interfere with adherence to the protocol procedures or
with the degree of tolerance to the IMP
- Known significant medical condition that may significantly impact the
intended transduction of the vector and/or expression and activity of the
protein, including but not limited to:
• Disseminated intravascular coagulation
• Accelerated fibrinolysis
• Advanced liver fibrosis (suggestive of or equal to METAVIR Stage 3
disease; e.g. a FibroScan™ score of =9 kPa is considered equivalent)
- Known history of an allergic reaction or anaphylaxis to factor IX
products
- Known uncontrolled allergic conditions or allergy/hypersensitivity to
any component of the IMP excipients
- Known history of allergy to corticosteroids
- Known medical condition that would require chronic administration of
steroids
- Previous gene therapy treatment
- Receipt of an experimental agent within 60 days prior to screening
- Current participation or anticipated participation within one year after
IMP administration in this trial in any other interventional clinical trial
involving drugs or devices.

1. Anamnesi di inibitori del fattore IX
2. Test degli inibitori del fattore IX risultato positivo allo screening e alla Visita L-finale (in base ai risultati del laboratorio locale)
3. Valori di laboratorio allo screening e alla Visita L-finale (in base ai risultati del laboratorio centrale):
a. ALT >2 volte il limite superiore della norma
b. Aspartato aminotransferasi (AST) >2 volte il limite superiore della norma
c. Bilirubina totale >2 volte il limite superiore della norma (tranne nei casi in cui tale valore sia causato da malattia di Gilbert)
d. ALP (Alkaline Phosphatase [Fosfatasi alcalina]) >2 volte il limite superiore della norma
e. Creatinina >2 volte il limite superiore della norma
4. Positività al test sierologico per il virus dell’HIV (Human Immunodeficiency Virus [immunodeficienza umana]) allo screening e alla Visita L-finale, non controllato con una terapia antivirale come dimostrato da conte dei linfociti CD4+ =200/µl (in base ai risultati del laboratorio centrale)
5. Infezione di epatite B o C con i seguenti criteri presenti allo screening:
i. terapia antivirale in corso di somministrazione per questa/e infezione/i

e/o
ii. positività per uno qualsiasi dei seguenti elementi (in base ai risultati del laboratorio centrale):
o antigene di superficie dell’epatite B (Hepatitis B surface Antigen, HBsAg) se, secondo il parere dello sperimentatore, ciò è dovuto a una precedente vaccinazione per l’epatite B piuttosto che a un’infezione di epatite B in fase attiva;
o acido desossiribonucleico del virus dell’epatite B (Hepatitis B Virus Deoxyribonucleic Acid, HBV DNA);
o acido ribonucleico del virus dell’epatite C (Hepatitis C Virus Ribonucleic Acid, HCV RNA).
7. 6. Disturbo della coagulazione noto diverso da emofilia B
8. Trombocitopenia, definita come una conta piastrinica <50 × 10¿/l, allo screening e alla Visita L-finale (in base ai risultati del laboratorio centrale)
9. Infezione grave nota o qualsiasi altra condizione medica concomitante, non controllata significativa, comprese, senza limitazione, malattia renale, epatica, cardiovascolare, ematologica, gastrointestinale, endocrina, polmonare, neurologica, cerebrale o psichiatrica, alcolismo, dipendenza da farmaci o qualsiasi altro disturbo psicologico che, secondo la valutazione dello sperimentatore, interferisce con l’aderenza alle procedure del protocollo o con il grado di tollerabilità dell’IMPCondizione medica significativa nota che potrebbe significativamente compromettere la trasduzione desiderata del vettore e/o l’espressione e l’attività della proteina, tra cui, ma non limitatamente a:
o coagulazione intravascolare disseminata;
o fibrinolisi accelerata;
o fibrosi epatica profonda (suggestiva di o equivalente a malattia allo stadio METAVIR 3; per es. un punteggio FibroScanTM =9 kPa è considerato equivalente).
10. Anamnesi nota di reazione allergica o anafilassi a prodotti a base di fattore IX
11. Anamnesi nota di allergia ai corticosterodi
13. 12. Condizioni allergiche non controllate o allergia/ipersensibilità note a qualsiasi componente degli eccipienti dell’IMP
14. Condizione medica nota che richiederebbe la somministrazione cronica di steroidi
15. Precedente somministrazione di una terapia genica
16. Assunzione di un agente sperimentale nei 60 giorni precedenti lo screening
Attuale partecipazione o partecipazione prevista entro un anno dopo la somministrazione dell’IMP in questa sperimentazione a qualsiasi altra sperimentazione clinica interventistica che preveda l’uso di farmaci o dispositivi.

E.5 End points

E.5.1

Primary end point(s)

Endogenous FIX activity after AMT-061 dosing

Attività di FIX endogeno

E.5.1.1

Timepoint(s) of evaluation of this end point

26 weeks after AMT-061 dosing.

26 settimane dopo la somministrazione di AMT-061

E.5.2

Secondary end point(s)

Secondary efficacy endpoints
- ABR comparison between AMT-061 and prophylaxis for non-inferiority
between the lead-in and the 52 week post-treatment (AMT-061) followup
-Annualized consumption of factor IX replacement therapy during the
52-week
post-treatment follow-up, excluding factor IX replacement for
invasive
procedures compared to the lead-in phase
-Proportion of subjects remaining free of previous continuous routine
prophylaxis
during the 52-week post-treatment follow-up
-Comparison of the percentage of subjects with trough factor IX activity
<12%
of normal between the lead-in phase and after treatment with
AMT-061
at Week 26
-Endogenous factor IX activity at 52 weeks after AMT-061 dosing
- ABR comparison between AMT-061 and prophylaxis for superiority
between the lead-in and the 52-week post-treatment (AMT-061) followup
-Rate of spontaneous (unprovoked) bleeding events during the 52-week
post-treatment
follow-up compared to lead-in phase
-Rate of joint bleeding events during the 52-week post-treatment
follow-up
compared to the lead-in phase
-Occurrence and resolution of target joints during the 52 weeks
following
AMT-061 dosing
-Correlation of factor IX activity levels during the 52-week posttreatment
follow-up with pre-IMP anti AAV5 antibody titers using the
luciferase
based NAB assay
-Rate of traumatic (provoked) bleeding events during the 52-week posttreatment
follow-up compared to the lead-in phase
-Patient reported outcome (PRO) questionnaires: EuroQol (EQ-5D-5L)
and
iPAQ
Secondary safety endpoints
- Adverse events
- Anti-AAV5 antibodies (total [IgM and IgG], neutralizing antibodies)
- AAV5 capsid-specific T cells
- Anti-factor IX antibodies
- Factor IX inhibitors
- Hematology and serum chemistry parameters
- ALT/AST levels, and corticosteroid use for ALT/AST increases
- Vector DNA in blood and semen
- Inflammatory markers: IL-1ß, IL-2, IL-6, IFN¿, MCP-1
- Alpha-fetoprotein (AFP)

Endpoint secondari di efficacia
- Confronto dell’ABR tra AMT-061 e la profilassi per la non inferiorità tra la fase di lead-in e il follow-up post-trattamento di 52 settimane (AMT-061)
- Consumo annualizzato della terapia sostitutiva con fattore IX durante il follow-up post-trattamento di 52 settimane, esclusa la terapia sostitutiva con fattore IX per procedure invasive rispetto alla fase di lead-in
- Percentuale di soggetti che rimangono liberi dalla precedente profilassi continua di routine durante il follow-up post-trattamento di 52 settimane
- Confronto della percentuale di soggetti con attività minima del fattore IX <12% del normale tra la fase di lead-in e dopo il trattamento con AMT-061 alla Settimana 26
- Attività del fattore IX endogeno a 52 settimane dopo la somministrazione di AMT-061
- Confronto dell’ABR tra AMT-061 e la profilassi per la superiorità tra la fase di lead-in e il follow-up post-trattamento di 52 settimane (AMT-061)
- Tasso di eventi di sanguinamento spontaneo (non provocato) durante il follow-up post-trattamento di 52 settimane rispetto alla fase di lead-in
- Tasso di eventi di sanguinamento articolare durante il follow-up post-trattamento di 52 settimane rispetto alla fase di lead-in
- Comparsa e risoluzione di articolazioni target durante le 52 settimane successive alla somministrazione di AMT-061
- Correlazione dei livelli di attività del fattore IX durante il follow-up post-trattamento di 52 settimane con titoli anticorpali anti-AAV5 pre-IMP usando il saggio dei NAB basato sulla luciferasi
- Tasso di eventi di sanguinamento traumatico (provocato) durante il follow-up post-trattamento di 52 settimane rispetto alla fase di lead-in
- Punteggi del questionario sugli esiti riferiti dal paziente (Patient Reported Outcome, PRO) dal Questionario internazionale sull’attività fisica (international Physical Activity Questionnaire, iPAQ)
- Punteggi del questionario sugli esiti riferiti dal paziente (PRO) dal Questionario europeo sulla qualità della vita a 5 dimensioni e 5 livelli (EuroQoL 5 Dimensions 5 Levels, EQ-5D-5L)
Endpoint di sicurezza secondari
- Eventi avversi (EA)
- Anticorpi anti-AAV5 (totali [IgM e IgG], NAB)
- Cellule T specifiche per il capside di AAV5
- Anticorpi anti-fattore IX
- Inibitori del fattore IX
- Parametri ematologici ed ematochimici
- Livelli di ALT/AST e uso di corticosteroidi per gli aumenti di ALT/AST
- DNA vettoriale nel sangue e nel liquido seminale
- Marcatori infiammatori: IL-1ß, IL-2, IL-6, IFN¿, MCP-1

E.5.2.1

Timepoint(s) of evaluation of this end point

Secondary efficacy endpoints - Comparison between 52-week post-treatment follow-up and the lead-in phase - Comparison between the lead-in phase and after treatment with AMT-061 at 26 &52 weeks - - During the 52-week post-treatment follow-up
- 52-week post-treatment follow-up compared to the lead-in phase
- Same as previous entry
- Same as previous entry
- Same as previous entry
- During 52 weeks following AMT-061 dosing
- During the 52-week post-treatment follow-up and pre-IMP anti-AAV5
antibody titers using the luciferase based NAB assay
- At 52 weeks after AMT-061 dosing
- Comparison between 52-week post-treatment follow-up and the lead-in
phase
Secondary safety endpoints
All will be monitored for the duration of the trial.

Endpoint secondari di efficacia
Confronto tra un follow-up post-trattamento di 52settimane e il lead-in fase
Confronto tra la fase di lead-in e dopo il trattamento con AMT- 061 a 26 e 52sett.
Durante il follow-up post-trattamento della durata di 52sett.
Come per la voce precedente
Come per la voce precedente
Come per la voce precedente
Durante 52sett- dopo la somministrazione di AMT-061
Durante il follow-up post-trattamento di 52settimane e anti-AAV5 pre-IMP titoli anticorpali usando il saggio NAB basato sulla luciferasi
A 52sett- dopo la somministrazione di AMT-061
Confronto tra un follow-up post-trattamento di 52 settimane e fase di lead-in
Endpoint di sicurezza secondari
Tutto verrà monitorato per la durata dello studio

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

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

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

in aperto

open label

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

Information not present in EudraCT

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

Canada

South Africa

United States

Belgium

Denmark

Finland

France

Germany

Ireland

Italy

Netherlands

Spain

Sweden

United Kingdom

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

LVLS

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

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

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)

F.1.1.6

Adolescents (12-17 years)

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)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

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

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

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)

After the post-treatment follow-up phase, subjects will enter a longterm follow-up phase for an additional 4 years to assess sustainability of efficacy and long-term safety.
Subjects are expected to:
- document factor IX usage & bleeding episode information
- visit the clinic every 6 months for evaluation of efficacy parameters & safety
- Complete joint health and questionnaires, every 12 months
AE occurrence will be continuously monitored (at least quarterly site staff/subject contact).

Dopo la fase di follow-up post-trattamento,i sogg. entreranno in una fase di follow-up a lungo termine per ulteriori 4anni per valutare la sostenibilità dell'efficacia e la sicurezza a lungo termine
I sogg. sono tenuti a:
Documentare l'utilizzo del fattore IX e informazioni sugli episodi di sanguinamento
visitare la clinica ogni 6mesi per la valutazione dei parametri di efficacia e sicurezza
(per il resto fare riferimento al 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

2019-02-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-03-12

P. End of Trial
P.	End of Trial Status	Completed

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Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
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