Clinical Trials Register

Summary
EudraCT Number:	2018-004179-11
Sponsor's Protocol Code Number:	2018-4898
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:	2021-08-17
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

2018-004179-11

A.3

Full title of the trial

Effectiveness of Somatostatin Analogues in Patients with hereditary hemorrhagic
telangiectasia and symptomatic gastrointestinal bleeding, SAIPAN-trial: a multicentre,
randomized, open-label, parallel-group, superiority trial.

Efficacia degli analoghi della somatostatina in pazienti con teleangiectasia emorragica
ereditaria e sanguinamento digestivo sintomatico, SAIPAN-trial: studio multicentrico,
randomizzato, open-label, a gruppi paralleli, trial di superiorità

A.3.1

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

Effectiveness of somatostatin analogues for GI bleeding in patients with hereditary
hemorrhagic telangiectasia

Efficacia degli analoghi della somatostatina nei sanguinamenti digestivi in pazienti
con teleangiectasia emorragica ereditaria

A.3.2

Name or abbreviated title of the trial where available

SAIPAN study

Studio SAIPAN

A.4.1

Sponsor's protocol code number

2018-4898

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	RADBOUD UNIVERSITY MEDICAL CENTER
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	ZonMw
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	Radboudumc
B.5.2	Functional name of contact point	Servizio Informazione sperimentazio
B.5.3	Address:
B.5.3.1	Street Address	Postbus 9101
B.5.3.2	Town/ city	Nijmegen
B.5.3.3	Post code	6500HB
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+310248187313
B.5.5	Fax number	+310243635129
B.5.6	E-mail	erwin.vangeenen@radboudumc.nl

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	Yes
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	octreotide a azione pronta 0,1 mg
D.3.2	Product code	[OCTREOTIDE ACETATO]
D.3.4	Pharmaceutical form	Concentrate for solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	OCTREOTIDE ACETATO
D.3.9.1	CAS number	83150-76-9
D.3.9.2	Current sponsor code	OPR00000697
D.3.9.4	EV Substance Code	SUB09417MIG
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	1
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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

Hereditary hemorrhagic telangiectasia (HHT), also known as Osler–Weber–Rendu disease
(in specific patients with gastrointestinal bleeding and transfusion dependency)

Teleangiectasia emorragica ereditaria HHT anche conosciuta come s. di rendu Osler
Weber , e che causa sanguinamento cronico digestivo in una parte degli affetti con
elevato fabbisogno trasfusionale

E.1.1.1

Medical condition in easily understood language

Patients suffering from HHT/Rendu-Osler-Weber disease and bleeding from the
stomach/bowel

Pazienti con HHT e sanguinamento cronico dal tubo digerente

E.1.1.2

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	PT
E.1.2	Classification code	10019883
E.1.2	Term	Hereditary haemorrhagic telangiectasia
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

To investigate the effectiveness of somatostatin analogues in decreasing the
transfusion requirements in patients with HHT and GI bleeding who are refractory to
endoscopic therapy.

Studiare l'efficacia degli analoghi della somatostatina nel ridurre il fabbisogno
trasfusionale in pazienti HHT con sanguinamento GI refrattari alla terapia
endoscopica.

E.2.2

Secondary objectives of the trial

To investigate the effectiveness of octreotide on: decreasing the endoscopic treatment
frequency, increasing the health-related quality of life, decreasing fatigue and
epistaxis symptoms, and to assess the effects of long-term octreotide on adverse
events and cost- effectiveness.

Studiare l'efficacia dell'octreotide su: diminuire la frequenza del trattamento
endoscopico, aumentare la qualità della vita , ridurre l'affaticamento e i sintomi
dell'epistassi e valutare gli effetti dell'octreotide a lungo termine sugli eventi
avversi e sull'efficacia economica.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

· Patients older than 18 years with written informed consent.
· Diagnosis of HHT: either confirmed by genetic testing or the Curaçao criteria
(definite diagnosis)
· Presence of endoscopic proven GI AVM manifestations / telangiectasias confirmed
within the last 12 months (upper and/or lower endoscopy and/or capsule endoscopy).
· Endoscopic refractory: at least 1 endoscopic APC, laser, or other endoscopic
treatment modality performed in the past 5 years.
· Substantial transfusion dependency: at least 4 blood units and / or intravenous
iron in the 6 months prior to study inclusion with:
o At least one serum ferritin below < 30 ug/l within the last 6 months requiring iron
infusion above or equal to 1 g and/or
o Haemoglobin below 5.6 mmol/l (9.0 g/dl) or are in need of transfusions due to anaemia
related symptoms within the last 6 months requiring blood transfusion above.

· Pazienti di età superiore ai 18 anni con consenso informato scritto.
· Diagnosi di HHT: confermata da test genetici o dai criteri curaçao (diagnosi
definita)
· Presenza di manifestazioni endoscopiche comprovate gi AVM / telangiectasie
confermate negli ultimi 12 mesi (endoscopia superiore e/o inferiore e/o endoscopia
capsula).
· Refrattarietà all' endoscopia: almeno 1 APC endoscopico, laser, o altre modalità di
trattamento endoscopico eseguite negli ultimi 5 anni.
· Dipendenza trasfusionale sostanziale: almeno 4 unità ematiche e/o ferro endovenoso
nei 6 mesi precedenti l'inclusione dello studio con:
o Almeno una ferritina sierica inferiore < 30 ug/l negli ultimi 6 mesi che richiedono
infusione di ferro superiore o uguale a 1 g e/o
o Emoglobina inferiore a 5,6 mmol/l (9,0 g/dl) o richiesta di trasfusioni a causa di
sintomi correlati all'anemia negli ultimi 6 mesi che richiedono trasfusioni di sangue

E.4

Principal exclusion criteria

· Liver cirrhosis Child-Pugh C,
· Insuloma,
· Uncontrolled diabetes mellitus as defined by HbA1c >64 mmol/ml, despite adequate
therapy
· Juvenile Polyposis Syndrome
· Symptomatic cholecystolithiasis (possible side-effect octreotide)

· Cirrosi epatica CHILD C
· Insulinoma,
diabete scompensato
poliposi giovanile
colecistolitiasi sintomatica

E.5 End points

E.5.1

Primary end point(s)

‘Successful response’, defined as a decrease of =50% in the amount of units
intravenous iron and/or blood transfusions given between the number of transfusions at
baseline (26 weeks prior to study inclusion) and during the treatment study period (26
weeks).
NB Patients included based on intravenous iron requirements and needing bloodtransfusion
during the study period are treatment failures.

diminuzione del =50% nella quantità di unità di ferro e/o trasfusioni di sangue
endovenose somministrate tra il numero di trasfusioni al basale (26 settimane prima
dell'inclusione dello studio) e durante il periodo di studio del trattamento (26
settimane).
I pazienti inclusi in base alla necessità di infusione di ferro per via endovenosa e
che necessitano di trasfusioni di sangue durante il periodo di studio sono considerati
fallimenti del trattamento.

E.5.1.1

Timepoint(s) of evaluation of this end point

26 weeks prior to study inclusion and during the treatment study period (26 weeks)

26 settimane prima dell'inclusione e durante il trattamento di 26 settimane

E.5.2

Secondary end point(s)

The percentual or mean/median difference between the half year prior to inclusion and
the treatment period of a half year between the treatment and observational arm in:
- blood and intravenous iron requirements
- number of endoscopic treatments
- cost-effectiveness (see economic evaluation)
The percentual or mean/median difference between the value at baseline and after a
half year between the treatment and observational arm in:
- PROMs: quality of life (SF-36), level of fatigue (multidimensional fatigue inventory
(MFI)-20), epistaxis severity (ESS tool), and patient satisfaction
The percentual or mean/median difference after a half year between the treatment and
observational arm in:
- (S)AE.
The percentual or mean/median difference between the value at baseline, after 4 weeks,
12 weeks, and after a half year between the treatment and observational arm in:
- hemoglobin and ferritin levels

La differenza percentuale o media/mediana tra il semestre precedente l'inclusione e il
periodo di trattamento di un semestre tra il trattamento e il braccio osservazionale
in:
- fabbisogno di sangue e ferro per via endovenosa
- numero di trattamenti endoscopici
- rapporto costo/efficacia (cfr. valutazione economica)
La differenza percentuale o media/mediana tra il valore al basale e dopo un semestre
tra il trattamento e il braccio osservazionale in:
- PROM: qualità della vita (SF-36), livello di affaticamento (inventario della fatica
multidimensionale (IFM)-20), gravità dell'epistassi (strumento ESS) e soddisfazione
del paziente
La differenza percentuale o media/mediana dopo un semestre tra il trattamento e il
braccio osservazionale in:
- (S)AE.
La differenza percentuale o media/mediana tra il valore al basale, dopo 4 settimane,
12 settimane e dopo un semestre tra il trattamento e il braccio osservazionale in:
- livelli di emoglobina e ferritina

E.5.2.1

Timepoint(s) of evaluation of this end point

0 weeks, 4 weeks, 12 weeks, 26 weeks, 30 weeks (follow up)

0-4-12-26-30 settimane

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

E.6.5

Efficacy

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

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

Yes

E.8.2.3.1

Comparator description

standard di cura

standard of care

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

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

Denmark

France

Germany

Netherlands

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

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

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)

patients will be followed up according to specific surveillance and treatment plans of
HHT

i pazienti proseguiranno la sorveglianza con trattamenti necessari secondo la presa in
carico specifica per HHT

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	NESSUNO
G.4.3.4	Network Country	Italy

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-09-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-06-21

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

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