Clinical Trials Register

Summary
EudraCT Number:	2019-004073-76
Sponsor's Protocol Code Number:	CAAA001A12401
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:	2020-10-21
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

2019-004073-76

A.3

Full title of the trial

A multicenter, open-label post authorization safety study to evaluate the effect of LysaKare® infusion on serum potassium levels in GEP-NET patients eligible for Lutathera® treatment

Uno studio di sicurezza post-autorizzazione in aperto, multicentrico per valutare l’effetto dell’infusione LysaKare ® sui livelli sierici di potassio in pazienti GEP-NET idonei al trattamento con Lutathera ®

A.3.1

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

Post-Authorization Safety Study (PASS) of LysaKare® in adult GEP-NET patients.

Studio di sicurezza post-autorizzazione (PASS) di LysaKare ® in pazienti GEP-NET adulti.

A.3.2

Name or abbreviated title of the trial where available

LysAA

A.4.1

Sponsor's protocol code number

CAAA001A12401

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	Advanced Accelerator Applications SA
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	Advanced Accelerator Applications SA
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Advanced Accelerator Applications International SA
B.5.2	Functional name of contact point	Clinical Operations
B.5.3	Address:
B.5.3.1	Street Address	4 rue de la tour de l'ile
B.5.3.2	Town/ city	Geneva
B.5.3.3	Post code	1204
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+41225190700
B.5.6	E-mail	regulatory_affairs@adacap.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	LysaKare
D.2.1.1.2	Name of the Marketing Authorisation holder	Advanced Accelerator Applications
D.2.1.2	Country which granted the Marketing Authorisation	France
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	LysaKare
D.3.2	Product code	[ATC LysaKare V03AF11]
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	Arginine
D.3.9.1	CAS number	1119-34-2
D.3.9.2	Current sponsor code	N/A
D.3.9.3	Other descriptive name	L-ARGININE HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB22706
D.3.10	Strength
D.3.10.1	Concentration unit	g gram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Lysine
D.3.9.1	CAS number	657-27-2
D.3.9.2	Current sponsor code	N/A
D.3.9.3	Other descriptive name	L-LYSINE HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB127503
D.3.10	Strength
D.3.10.1	Concentration unit	g gram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
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

LysaKare® is indicated for reduction of renal radiation exposure during peptide-receptor radionuclide therapy (PRRT) with lutetium (177 Lu) oxodotreotide in adults.

LysaKare® è indicato per la riduzione dell’esposizione renale alle radiazioni durante la terapia recettoriale con peptidi radiomarcati (PRRT) con lutezio (177Lu) oxodotreotide in adulti.

E.1.1.1

Medical condition in easily understood language

LysaKare® is indicated for kidney protection during cancer treatment with lutetium (177 Lu) oxodotreotide in adults.

LysaKare® è indicato per la protezione dei reni durante il trattamento del cancro con lutezio (177 Lu) oxodotreotide negli adulti.

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	20.0
E.1.2	Level	SOC
E.1.2	Classification code	10038359
E.1.2	Term	Renal and urinary disorders
E.1.2	System Organ Class	10038359 - Renal and urinary disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	PT
E.1.2	Classification code	10029140
E.1.2	Term	Nephritis radiation
E.1.2	System Organ Class	10022117 - Injury, poisoning and procedural complications

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	PT
E.1.2	Classification code	10029140
E.1.2	Term	Nephritis radiation
E.1.2	System Organ Class	10022117 - Injury, poisoning and procedural complications

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the effect of LysaKare® administration on serum potassium concentrations in GEP-NET patients eligible for Lutathera® treatment

Valutare l’effetto della somministrazione di LysaKare® sulla concentrazione sierica di potassio in pazienti GEP-NET idonei al trattamento con Lutathera®

E.2.2

Secondary objectives of the trial

To confirm the safety profile of LysaKare® infusion in GEP-NET patients eligible for Lutathera® treatment, without co-administration of Lutathera®

Confermare il profilo di sicurezza dell’infusione di LysaKare® in pazienti GEP-NET idonei al trattamento con Lutathera® senza co-somministrazione di Lutathera®

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female patients with somatostatin receptor positive gastroenteropancreatic neuroendocrine tumours (GEP-NETs), who are eligible for the treatment with Lutathera® as per Lutathera® label indication.
2. Age =18 years.
3. Patients who have provided a signed informed consent form to participate in the study, obtained prior to the start of any protocol related procedures.

1. Pazienti di sesso maschile o femminile con tumori neuroendocrini gastroenteropancreatici (GEP-NET) positivi per i recettori della somatostatina, idonei per il trattamento con Lutathera® secondo l'indicazione terapeutica di Lutathera®.
2. Età =18 anni.
3. Pazienti che hanno fornito un modulo di consenso informato firmato per partecipare allo studio, ottenuto prima dell’inizio di qualsiasi procedura correlata al protocollo.

E.4

Principal exclusion criteria

1. Pre-existing hyperkalemia (>6.0 mmol/L at screening) if not adequately corrected before starting the LysaKare® infusion.
2. Instances when Lutathera® is not recommended per the Lutathera® SmPC:
a. Uncontrolled congestive heart failure (NYHA III, IV);
b. Kidney failure with creatinine clearance < 50 mL/min calculated by the Cockroft Gault method;
c. Impaired haematological function with either Hb < 4.9 mmol/L (8 g/dL), platelets < 75 G/L (75x103/mm3), or leucocytes < 2 G/L (2,000/mm3) (except lymphopenia);
d. Liver impairment with either total bilirubinemia > 3 times the upper limit of normal or albuminemia < 30 g/L and prothrombin ratio decreased < 70%.
3. Pregnancy or lactation, positive pregnancy test at screening or pre-dose based on the contraindication for Lutathera®.
4. Hypersensitivity to the IMP active substances.
5. Any significant medical or social condition which may interfere with the subject’s ability to comply with the study visit schedule or the study assessments.
6. Patients who have received any investigational agent within the last 30 days.
7. Patients that have received a dose of Lutathera® prior to the screening visit or are scheduled for Peptide Receptor Repeat (PRRT) treatment within 7 days of the study infusion of LysaKare®.

1. Ipercaliemia pre-esistente (>6,0 mmol/L allo screening) se non adeguatamente corretta prima dell’inizio dell’infusione di LysaKare®.
2. Casi in cui Lutathera® non è raccomandato secondo l’RCP di Lutathera®:
a. Insufficienza cardiaca congestizia non controllata (NYHA III, IV);
b. Insufficienza renale con clearance della creatinina <50 mL/min calcolata con il metodo Cockroft Gault;
c. Funzione ematologica compromessa con Hb <4,9 mmol/L (8 g/dL), piastrine <75 G/L (75x103/mm3) o leucociti <2 G/L (2,000/mm3) (a eccezione di linfopenia);
d. Insufficienza epatica con bilirubinemia totale >3 volte il limite superiore della norma o albuminemia <30 g/L e rapporto di tempo protrombinico ridotto <70%.
3. Gravidanza o allattamento, test di gravidanza positivo allo screening oppure pre-dose in base alle controindicazioni per Lutathera®.
4. Ipersensibilità ai principi attivi dell’IMP.
5. Qualsiasi condizione clinica o sociale significativa che potrebbe interferire con la capacità del soggetto di rispettare il programma delle visite dello studio o le valutazioni dello studio.
6. Pazienti che hanno ricevuto qualsiasi agente sperimentale entro gli ultimi 30 giorni.
7. Pazienti che hanno ricevuto una dose di Lutathera® prima della visita di screening o per cui è stata programmata una terapia recettoriale con peptidi radiomarcati (PRRT) entro 7 giorni dall’infusione di LysaKare® prevista dallo studio.

E.5 End points

E.5.1

Primary end point(s)

Change in serum potassium levels at specified time points after LysaKare® IV administration compared to baseline.

Cambiamento dei livelli sierici di potassio a tempi specifici dopo la somministrazione di LysaKare® IV rispetto alla linea di base

E.5.1.1

Timepoint(s) of evaluation of this end point

2 h, 4 h, 6 h, 8 h, 12 h, 24 h

E.5.2

Secondary end point(s)

- Incidence of LysaKare® related adverse events
- Changes in vital signs and ECG parameters
- Change in laboratory parameters

- Incidenza di eventi avversi correlati a LysaKare®
- Cambiamenti nei segni vitali e nei parametri ECG
- Modifica dei parametri di laboratorio

E.5.2.1

Timepoint(s) of evaluation of this end point

2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h

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

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)

E.7.4

Therapeutic use (Phase IV)

Yes

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

Aperto

Open

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

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 the trial occurs after the 48 h follow-up call of the last patient treated.

La fine della sperimentazione si considera dopo la chiamata di follow-up a 48 ore dell'ultimo paziente trattato.

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

Yes

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2020-10-21.

Yes

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

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)

None

Nessuno

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

2020-08-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-07-22

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-03-22

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