Clinical Trials Register

Summary
EudraCT Number:	2015-003318-26
Sponsor's Protocol Code Number:	AS/NEPA/001
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:	2021-09-09
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

2015-003318-26

A.3

Full title of the trial

Phase II, open-label, not comparative, multicenter study of multiple doses of NEPA (Netupitant+Palonosetron) in preventing chemotherapy induced nausea and vomiting
(CINV) in patient with Non Hodgkin’s Lymphoma
receiving salvage chemotherapy followed by high dose chemotherapy and autologous hematopoietic stem cells support.

Studio di fase II, in aperto, non comparativo, multicentrico, di dosi ripetute di NEPA (netupitant + palonosetron) nella prevenzione della nausea ed il vomito indotti da chemioterapia (CINV) in pazienti con Linfoma Non-Hodgkin trattati con chemioterapia di salvataggio seguita da alte dosi di chemioterapia con supporto di cellule staminali ematopoietiche

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

AS/NEPA/001

A.4.1

Sponsor's protocol code number

AS/NEPA/001

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	ASSOCIAZIONE SALENTINA ANGELA SERRA ONLUS
B.1.3.4	Country	Italy
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	ITALFARMACO S.P.A.
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	U.O. EMATOLOGIA - P.O. VITO FAZZI
B.5.2	Functional name of contact point	TRIALS OFFICE
B.5.3	Address:
B.5.3.1	Street Address	PIAZZA F.MURATORE - IV PIANO POLO ONCOLOGICO
B.5.3.2	Town/ city	LECCE
B.5.3.3	Post code	73100
B.5.3.4	Country	Italy
B.5.4	Telephone number	0832661923
B.5.5	Fax number	0832661923
B.5.6	E-mail	quinta.ematolecce@gmail.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	Yes
D.2.1.1.1	Trade name	AKYNZEO
D.2.1.1.2	Name of the Marketing Authorisation holder	HELSINN BIREX PHARMACEUTICALS Ltd
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	AKYNZEO
D.3.2	Product code	EU/1/15/1001/001
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
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

NON HODGKIN'S LYMPHOMA

LINFOMA NON HODGKIN

E.1.1.1

Medical condition in easily understood language

NON HODGKIN'S LYMPHOMA

LINFOMA NON HODGKIN

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	24.0
E.1.2	Level	LLT
E.1.2	Classification code	10067070
E.1.2	Term	Follicular B-cell non-Hodgkin's lymphoma
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary endpoint is the percentage of patients achieving a complete response (defined as no vomiting and no use of rescue medication) during the Conditioning Chemotherapy regimen (BEAM/FEAM). The period of assessment
of the primary endpoint will be the overall phase, defined from day 1 (first day of chemotherapy) until 48 hours after the last dose of chemotherapy.

Valutare il numero di pazienti che ottengono una risposta completa, definita come assenza di episodi di vomito o di impiego di medicazioni antiemetiche, durante la chemioterapia di
condizionamento BEAM/FEAM, misurata per l’intero periodo di rischio di CINV (corrispondente
ai giorni di somministrazione di chemioterapia BEAM o FEAM, e le 48 ore successive
all’ultima dose di chemioterapia).

E.2.2

Secondary objectives of the trial

Secondary endpoints are During the Running Phase MD-CT and During the Study Phase (MD- HD-CT) - Complete Response, defined as no vomiting and no need for rescue medication; Complete Control (defined as Complete Response with no more than mild nausea); Percentage of emesis-free patients (no emetic episodes); Presence of nausea graded according to Likert scale (none, mild, moderate and severe); Patient global satisfaction with antiemetic therapy, as
measured by a visual analogue scale (VAS); Those endpoints will evaluated during the acute phase (days of MD-CTadministration), during the delayed phase (up to 48 hours after the last dose of
MD-CT) and during each single day of each course of multiple day salvage
chemotherapy.
During the running phase the following endpoints will be also evaluated. Cube score assessment before MD-CT administration
(38) Appendix 3 - Efficacy of the mobilization, as number of aphaeresis,number of CD34+ collected, number and type of G-CSF used and use of Pler

Saranno valutati durante la fase di "running" (MD-CT) e durante la fase di studio (BEAM/FEAM), la risposta completa (definita come assenza di vomito o di impiego di medicazioni antiemetiche), il controllo completo (definito come risposta completa e non più di nausea lieve), le percentuali di pazienti liberi da emesi (nessun episodio emetico), la percentuale di nausea secondo la scala Likert, il livello di soddisfazione dei pazienti alla terapia antiemetica misurata tramite una scala visiva analogica e la sicurezza.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Patients 18 years of age or older deemed eligible to undergo autologous peripheral stem cell transplant;
• Diagnosis of non-Hodgkin lymphoma
• Preparative regimen consisting of BEAM or FEAM (see section 3.3)
• Multiple-day salvage chemotherapy regimen lasting at least 3 days and no more than 6 days.
• ECOG 0-2
• Written informed consent
• Patient must be able to complete the patient’s diary.

- Pazienti con età maggiore uguale a 18 anni ritenuti idonei a subire un trapianto autologo di
cellule staminali periferiche.
- Diagnosi di linfoma non-Hodgkin.
- Regime di condizionamento costituito da BEAM o FEAM ( vedere la sezione 3.3).
- Regime di chemioterapia di salvataggio a giorni multipli della durata di almeno 3 giorni e
non più di 6 giorni.
- ECOG 0-2 .
- Consenso informato scritto.
- Il paziente deve essere in grado di compilare il proprio diario giornaliero.

E.4

Principal exclusion criteria

• Prior treatment with investigational medications in 30 days before selection
• Nausea and vomiting at baseline
• Chronic use of other antiemetic agent(s)
• Patients who are unable to take oral medication (e.g. due to tumor obstruction)
• Gastrointestinal obstruction or active peptic ulcer
• Radiation therapy to pelvis or abdomen within 1 week before or after study day 1
• Allogeneic stem cell transplant
• Inadequate organ function defined as: Aspartate transaminase (AST) > 3 x upper limit of normal (ULN); Alanine transaminase (ALT) > 3x ULN; Bilirubin > 3x ULN; Alkaline phosphatase > 3x ULN; Creatinine > 2 mg/dL
• Documented or known hypersensitivity to 5HT3-RA, NK1-RA, or to any component of NEPA
• Pregnant or lactating women
• Uncontrolled Diabetes Mellitus or other uncontrolled concomitant diseases
• Prior malignancies at other sites except surgically treated non-melanoma skin cancer, prostate cancer, superficial cervical cancer, or other cancer from which the patient had been disease-free for = 5 years
• Myocardial infarction within the past 6 months
• Psychiatric or CNS disorders interfering with ability to comply with study protocol.

- Precedente trattamento con farmaci sperimentali nei 30giorni antecedenti la selezione.
- Nausea e vomito presenti alla baseline.
- Uso cronico di altri agenti antiemetici.
- Pazienti non in grado di assumere farmaci per via orale (per esempio per la presenza di
ostruzioni tumorali).
- Ostruzione gastrointestinale o ulcera peptica attiva.
- Terapia radiante in regione pelvica o addominale entro 1 settimana precedente o a seguire il
giorno 1 dello studio.
- Trapianto allogenico di cellule staminali.
- Funzioni organiche inadeguate, definite come: Aspartato-transaminasi (AST) > 3x al di
sopra del limite di normalità (ULN, upper limit of normal); Alanin- transferasi (ALT) > 3x
ULN; Bilirubina > 3x ULN; Fosfatasi alcalina > 3x ULN; Creatinina > 2 mg/dL.
- Ipersensibilità documentata o nota a 5HT3-RA, NK1-RA o a qualsiasi componente di NEPA.
- Donne in stato di gravidanza o di allattamento al seno.
- Diabete mellito non controllato o altre patologie concomitanti instabili.
- Precedenti tumori in altri siti ad eccezione di quelli trattati chirurgicamente, come cancri cutanei di natura non melanomatosa, cancri della prostata, cancri cervicali superficiali , o altri per cui sia stato documentato uno stato di eradicazione da = 5 anni.
- Infarto miocardico entro i 6 mesi precedenti.
- Disordini psichiatrici o del Sistema Nervoso Centrale (CNS) che possano interferire con la possibilità di aderire alle richieste del protocollo di studio.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is the percentage of patients achieving a complete response (defined as no vomiting and no use of rescue medication) during the Conditioning Chemotherapy regimen (BEAM/FEAM).

E.5.1.1

Timepoint(s) of evaluation of this end point

The period of assessment
of the primary endpoint will be the overall phase, defined from day 1 (first day of chemotherapy) until 48 hours after the last dose of chemotherapy.

L'endpoint primario sarà misurato per l’intero periodo di rischio di CINV (corrispondente
ai giorni di somministrazione di chemioterapia BEAM o FEAM, e le 48 ore successive
all’ultima dose di chemioterapia).

E.5.2

Secondary end point(s)

will be evaluated during “Running” phase (MD-CT) and during “Study” phase (BEAM/FEAM), according to the following scheme.
Complete response, Complete control, Percentage of emesis-free patients, Percentage of nausea graded according to Likert scale, Patient global satisfaction with antiemetic therapy, as measured by a visual analogue scale (VAS)

saranno valutati durante la fase di “Running” (MD-CT) e durante la fase di “Studio” (BEAM/FEAM).
Risposta completa, Controllo completo, Percentuali di pazienti liberi da emesi, Percentuale di nausea secondo la scala Likert, Valutare il livello di soddisfazione dei pazienti alla terapia antiemetica, misurata tramite una scala visiva analogica.
Dal primo giorno di chemioterapia di condizionamento (BEAM/FEAM) fino ai 7 giorni dopo
l’ultima dose: Percentuali di pazienti liberi da emesi (nessun episodio emetico), Percentuale di nausea secondo la scala Likert (no, lieve, moderata e severa), Valutare il livello di soddisfazione dei pazienti alla terapia antiemetica, misurata
tramite una scala visiva analogica (visual analogue scale)

E.5.2.1

Timepoint(s) of evaluation of this end point

From the first day of chemotherapy (BEAM/FEAM) until 7 days after the last dose

Dal primo giorno di chemioterapia fino ai 7 giorni dopo l’ultima dose

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

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

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.8.3

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

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

The end of study will be 30 days after the last dose of study medication: LVLS.

La sperimentazione si concluderà 30 giorni dopo l'ultima somministrazione di farmaco sperimentale all'ultimo paziente che coincide con 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)

NOT APPLICABLE

NON APPLICABILE

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

2015-12-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-09-22

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

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