Clinical Trials Register

Summary
EudraCT Number:	2017-001366-14
Sponsor's Protocol Code Number:	207757
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:	2020-02-04
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

2017-001366-14

A.3

Full title of the trial

A long-term safety and efficacy follow-on study in participants with transfusion dependent β-thalassemia who have previously received GSK2696277 (autologous hematopoietic stem cells genetically modified with GLOBE lentiviral vector encoding for the human beta-globin gene) and completed the TIGET-BTHAL study.

Studio di Follow on sulla sicurezza e sull’efficacia a lungo termine in soggetti con Betatalassemia
trasfusione dipendente che sono stati trattati in precedenza con GSK2696277 (cellule staminali emopoietiche autologhe
geneticamente modificate con vettore lentivirale GLOBE che codifica per il gene umano della beta globina) e che hanno completato lo
studio TIGET-BTHAL

A.3.1

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

A follow-on study in patients who have received gene therapy for Beta-thalassemia in the TIGET-BTHAL study to assess safety and effectiveness of treatment.

Uno studio successivo su pazienti che
hanno ricevuto terapia genica per la beta-talassemia nello studio TIGET-BTHAL per valutare la sicurezza e l'efficacia del trattamento

A.3.2

Name or abbreviated title of the trial where available

GSK2696277, P2b, beta-thalassemia patient safety follow-on to TIGET BTHAL study

GSK2696277, Studio di fase 2, di follow on sulla sicurezza in pazienti con beta talassemia che hanno

A.4.1

Sponsor's protocol code number

207757

A.5.4

Other Identifiers

Name:

Number:

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	GLAXOSMITHKLINE RESEARCH AND DEVELOPMENT
B.1.3.4	Country	United Kingdom
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	GlaxoSmithKline Research & Development Limited
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	GlaxoSmithKline research & Development Limited
B.5.2	Functional name of contact point	GSK clinical Support HelpDesk
B.5.3	Address:
B.5.3.1	Street Address	1-3 Iron Bridge road, Stockley Park West
B.5.3.2	Town/ city	Uxbridge, Middlesex
B.5.3.3	Post code	UB11 1BT
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	00440209904466
B.5.5	Fax number	00440209904968
B.5.6	E-mail	GSKClinicalSupportHD@GSK.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	EMA/OD/024/16
D.3 Description of the IMP
D.3.1	Product name	NA
D.3.2	Product code	NA
D.3.4	Pharmaceutical form	Suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	NA
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0
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

Beta-thalassemia

Beta talassemia

E.1.1.1

Medical condition in easily understood language

Beta-thalassemia

Beta talassemia

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	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10054660
E.1.2	Term	Thalassemia beta
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

•To evaluate the risks associated with gene therapy during long-term follow up of participants with transfusion dependent beta-thalassemia who have participated in TIGET-BTHAL

Valutare i rischi a lungo termine associati alla terapia genica durante il follow-up (FU) a lungo termine in soggetti con beta-talassemia trasfusione dipendente che hanno partecipato allo studio TIGET-BTHAL

E.2.2

Secondary objectives of the trial

•To determine the long-term efficacy of GSK2696277 on disease parameters in participants with transfusion dependent beta-thalassemia who have participated in TIGET-BTHAL

•To evaluate the long-term safety in participants with transfusion dependent beta-thalassemia who have participated in TIGET-BTHAL

•To evaluate the long-term impact on quality of life of GSK2696277 in participants with transfusion dependent beta-thalassemia who have participated in TIGET-BTHAL

•To evaluate development in paediatric participants with transfusion dependent beta-thalassemia who have participated in TIGET-BTHAL.

- Stabilire l’efficacia a lungo termine di GSK2696277 sui parametri della malattia in soggetti con betatalassemia trasfusione dipendente che hanno partecipato allo studio TIGET-BTHAL - Valutare la sicurezza a lungo termine in soggetti con beta-talassemia trasfusione dipendente che hanno partecipato allo studio TIGET-BTHAL - Valutare l’impatto a lungo
termine sulla qualità della vita di GSK2696277 in soggetti con beta-talassemia trasfusione dipendente che hanno partecipato allo
studio TIGET-BTHAL - Valutare lo sviluppo dei soggetti pediatrici con beta-talassemia trasfusione dipendente che hanno partecipato allo studio TIGET-BTHAL

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Participants are eligible to be included in the study only if all of the following criteria apply:
1.Participants who have completed study TIGET-BTHAL i.e. who have received treatment and been followed for two years post treatment with GSK2696277.
2.For adults; capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. For children; informed assent and/or consent in writing signed by the subject and/or parent(s) / legal representative (according to local regulations and age of the subject).

Saranno inclusi i questo studio soggetti che:
1. hanno completato lo studio TIGET-BTHAL, e più precisamente hanno ricevuto il trattamento e sono stati seguiti per due anni dopo il trattamento con GSK2696277.
2. sono in grado di fornire il proprio consenso in linea con quanto descritto nell’Appendice 2 del protocollo (soggetti adulti) oppure sono in grado di fornire un assenso firmato in conformità alla normativa e all’età del soggetto e per i quali sia stato ottenuto un consenso firmato dai genitori/tutore legale (soggetti pediatrici.)

E.4

Principal exclusion criteria

None

Non sono previsti

E.5 End points

E.5.1

Primary end point(s)

Absence of lentiviral gene-therapy specific
safety issues, as evidenced by: •Absence of abnormal clonal proliferation (ACP) •Polyclonal engraftment (integration sites)

Assenza di problemi di sicurezza specifici legati alla terapia genica lentivirale, come evidenziato da:
•Assenza di proliferazione clonale anomala (Abnormal Clonal Proliferation, ACP)
•Attecchimento policlonale (siti di integrazione)

E.5.1.1

Timepoint(s) of evaluation of this end point

Yearly for six years

Annualmente per sei anni

E.5.2

Secondary end point(s)

Reduction in Red Blood Cell (RBC)
transfusion volume compared to pre-gene therapy(GT) in TIGET-BTHAL •Reduction in transfusion frequency up to transfusion
independence compared to pre-GT in TIGET-BTHAL •Transfusion independence •Hemoglobin levels in participants who achieve
transfusion independence. •Sustained engraftment of genetically corrected cells as defined by a Vector Copy Number (VCN)≥
0.15/genome in bone marrow erythroid cells •Survival •Incidence and severity of adverse events •Laboratory parameters •Quality
of life as measured by; Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT BMT) and Short-form-36 (SF-36)
for adults and PedsQL quality of life for pediatric participants •Growth (height; absolute, percentile. vs predicted genetic height) -
Hormones (thyroid function, sex hormones, pancreatic function, cortisol) -Puberty

•Riduzione del volume trasfusionale degli eritrociti (RBC) rispetto ai parametri pre-terapia genica
(Gene Therapy, GT) somministrata nell’ambito dello studio TIGET-BTHAL
•Riduzione della frequenza delle trasfusioni fino all’indipendenza dalla trasfusione rispetto ai parametri pre-GT nell’ambito dello
studio TIGET-BTHAL
•Indipendenza dalla trasfusione
•Livelli di emoglobina nei soggetti che raggiungono l’indipendenza dalla trasfusione.
•Attecchimento mantenuto/riuscito di cellule geneticamente corrette come definito dal numero di copie di vettore (VCN) per
cellule eritroide ≥ 0,15
•Sopravvivenza
•Incidenza e gravità degli eventi avversi
•Parametri degli esami di laboratorio
Qualità della vita misurata con i questionari Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT BMT) e
Short-form-36 (SF-36) nei soggeti adulti e con il questionario PedsQL nei soggetti pediatrici
Crescita: altezza assoluta e percentile vs altezza geneticamente prevista, ormoni (Funzione tiroidea, ormoni sessuali, funzione
pancreatica, cortisolo) - Pubertà

E.5.2.1

Timepoint(s) of evaluation of this end point

Yearly for six years

Annualmente per sei anni

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)

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

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

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

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.7

Trial has a data monitoring committee

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

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)

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

Yes

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

Yes

F.3.3.7.1

Details of other specific vulnerable populations

Children

Minori

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)

Following the study, participants will be managed for their disease, as appropriate, according to their local clinical practice. Additional follow-up information may be collected via a patient registry following any regulatory approval, depending on regulatory requirements.

Al
termine dello studio i soggetti saranno gestiti per la loro malattia in linea con la pratica clinica locale. Ulteriori informazioni di
follow-up potranno essere raccolte attraverso un registro pazienti previa eventuale approvazione regolatoria, in base ai requisiti
normativi

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

2017-07-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-09-14

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

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