Clinical Trials Register

Summary
EudraCT Number:	2012-002920-33
Sponsor's Protocol Code Number:	CLI00076
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:	2012-10-16
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

2012-002920-33

A.3

Full title of the trial

A Randomized Controlled Study to Evaluate Efficacy and Safety of S-303 Treated Red Blood Cells in Subjects with Thalassemia Major Requiring Chronic RBC Transfusion

Studio controllato randomizzato per valutare l'efficacia e la sicurezza degli eritrociti trattati con S 303 in soggetti affetti da talassemia major che necessitano di trasfusioni croniche di eritrociti

A.3.1

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

A Randomized Controlled Study to Evaluate Efficacy and Safety of S-303 Treated Red Blood Cells in Subjects with Thalassemia Major Requiring Chronic RBC Transfusion

A.4.1

Sponsor's protocol code number

CLI00076

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	CERUS CORPORATION
B.1.3.4	Country	United States
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	Cerus Corporation
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Cerus Corporation
B.5.2	Functional name of contact point	Regulatory Affairs
B.5.3	Address:
B.5.3.1	Street Address	2550 STANWELL DRIVE
B.5.3.2	Town/ city	CONCORD, CALIFORNIA
B.5.3.3	Post code	94520
B.5.3.4	Country	United States
B.5.4	Telephone number	+1.925.288.6000
B.5.5	Fax number	+1.925.288.0190
B.5.6	E-mail	cmoore@cerus.con

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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	S-303 Treated Red Blood Cells in SAG-M
D.3.2	Product code	NA
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.3.9.1	CAS number	210584-54-6
D.3.9.2	Current sponsor code	AMRI-21810300
D.3.9.3	Other descriptive name	S-303 2HCl
D.3.10	Strength
D.3.10.1	Concentration unit	g gram(s)
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	600
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	RED BLOOD CELLS, LEUKOCYTES REDUCED
D.3.9.3	Other descriptive name	Red blood cells for transfusion
D.3.9.4	EV Substance Code	SUB15116MIG
D.3.10	Strength
D.3.10.1	Concentration unit	g gram(s)
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	600
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)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
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	Yes
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.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Packed red blood cells in SAG-M additive (preservative) solution
D.3.2	Product code	NA
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	RED BLOOD CELLS, LEUKOCYTES REDUCED
D.3.9.3	Other descriptive name	Standard red blood cells components for transfusion
D.3.9.4	EV Substance Code	SUB15116MIG
D.3.10	Strength
D.3.10.1	Concentration unit	g gram(s)
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	600
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)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
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	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	Yes
D.3.11.13.1	Other medicinal product type	Red blood cells components for transfusion

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

Subjects with Thalassemia Major Requiring Chronic RBC Transfusion

Soggetti con talassemia major che necessitano di trasfusioni croniche di eritrociti

E.1.1.1

Medical condition in easily understood language

Thalassemia Major patients requiring periodic transfusion of red blood cells for disease management.

Pazienti con talassemia major che necessitano di trasfusioni periodiche di globuli rossi per la gestione della malattia.

E.1.1.2

Therapeutic area

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

MedDRA Classification

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 objectives of this study are to evaluate the efficacy and safety of S 303 treated RBCs in subjects who require chronic transfusion support due to thalassemia major

L'obiettivo dello studio è di valutare l'efficacia e la sicurezza degli eritrociti trattati con S-303 nei soggetti affetti da talassemia major

E.2.2

Secondary objectives of the trial

N/A

Non previsti

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Age >= 10 years, of either gender - Diagnosed with thalassemia major and currently participating in a chronic transfusion program - At least a one year history of chronic RBC transfusion support with a stable transfusion requirement (per treating physician) - Intervals of at least 14 days between RBC transfusions - All RBC components are given on one day for each transfusion episode - Negative direct antiglobulin tests (DAT) - Stable iron chelation regimen - Available for measurement of hemoglobin level at one hour post transfusion - Signed and dated informed consent form

- Età >= 10 anni, di entrambi i sessi -Diagnosi di talassemia major e attuale partecipazione a un programma di trasfusione cronica - Almeno un anno di supporto trasfusionale cronico di eritrociti con fabbisogno trasfusionale stabile (secondo le indicazioni del medico curante) - Intervalli di almeno 14 giorni fra le trasfusioni di eritrociti - Tutti i componenti eritrocitari vengono forniti in un giorno per ogni episodio trasfusionale - Test antiglobulina diretto (DAT) negativo - Stabile terapia chelante del ferro - Disponibile per la misurazione del livello di emoglobina un`ora dopo la trasfusione - Modulo di consenso informato firmato e datato

E.4

Principal exclusion criteria

- Baseline antibody specific to S-303 treated RBC (positive test, as defined in Section 8.4.1) - Evidence of splenic hyper function defined as a transfusion requirement >180 cc/kg/year (at 100% hematocrit) - Splenic enlargement: spleen palpable ≥4 cm below costal margin - Alloimmunization to minor blood group antigens to the extent that the ready provision of compatible blood may not be feasible for the study (alloimmunization alone is not an automatic exclusion) - Current specialized treatment with washed or frozen RBC Requirement for gamma irradiated RBC components (would present blinding difficulty due to blood component labeling regulations - Treatment with any medication that is known to adversely affect RBC viability - HIV or HCV infection (defined as RNA positive) - Pregnant or breast feeding female, or female of child-bearing potential not using a medically approved form of contraception - Acute or chronic medical disorder other than thalassemia that, in the opinion of the Investigator or medical monitor, may prevent the subject from completing participation in the study - Participation in another clinical study, either concurrently or within the previous 28 days, in which the study drug or device may influence red blood cell viability

- Baseline con anticorpo specifico agli eritrociti trattati con S 303 (test positivo) - Evidenza di iperfunzione splenica definita come fabbisogno trasfusionale >180 cc/kg/anno (al 100% ematocrito) - Ingrossamento della milza: milza palpabile ≥4 cm al di sotto del margine costale - Alloimmunizzazione agli antigeni dei gruppi sanguigni minori nella misura in cui la fornitura di sangue compatibile potrebbe non essere fattibile per lo studio (l'alloimmunizzazione da sola non comporta automaticamente l'esclusione) - Attuale trattamento specializzato con eritrociti lavati o congelati - Necessità di componenti eritrocitari irradiati con raggi gamma (presenta difficoltà a causa della normativa concernente l'etichettatura degli emocomponenti) - Trattamento con qualsiasi medicinale noto per la sua capacità di influire negativamente sulla vitalità degli eritrociti - Infezione da HIV o HCV (definito come RNA positivo) - Donne in gravidanza o allattamento al seno oppure donne in età fertile che non utilizzano alcuna forma di contraccezione clinicamente approvata - Disturbo medico acuto o cronico diverso dalla talassemia che, a giudizio del ricercatore o del medico, possa impedire al soggetto di completare la partecipazione allo studio - Partecipazione ad un altro studio clinico, contemporaneamente o nei 28 giorni precedenti, in cui il farmaco o il dispositivo dello studio possano influenzare la vitalità degli eritrociti

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is: - Hemoglobin consumption measured as total hemoglobin mass transfused per subject adjusted for average body weight and the number of days during the efficacy evaluation period (adjusted Hgb consumption units are g Hgb/kg body weight/day). The primary safety endpoint is: - Incidence of a treatment-emergent antibody with confirmed specificity to S-303 treated RBC associated with clinically significant hemolysis

Endpoint primario di efficacia: - Il consumo di emoglobina espresso in massa totale di emoglobina trasfusa per soggetto in base al peso corporeo medio e il numero di giorni durante il periodo di valutazione dell'efficacia (le unità di consumo di Hgb regolate sono g Hgb/kg peso corporeo/giorno). Endpoint primario di sicurezza: - Incidenza di un anticorpo emergente dal trattamento con specificità confermata agli eritrociti trattati con S 303 associata ad emolisi clinicamente significativa

E.5.1.1

Timepoint(s) of evaluation of this end point

Study participation is expected to require approximately 12 months.

La partecipazione allo studio per ogni paziente dovrebbe essere di circa 12 mesi.

E.5.2

Secondary end point(s)

Secondary Efficacy Endpoints The secondary efficacy endpoints are:  Hemoglobin increment one hour post-transfusion  Proportional decline in post transfusion hemoglobin level per day (%/day) The secondary safety endpoints are: - Adverse events - Transfusion reactions within 24 hours of a study transfusion with the assigned study product - Frequency of allo-immunization to RBC allo-antigens

Endpoint secondari di efficacia: - Incremento dell'emoglobina un'ora (1H) dopo la trasfusione - Riduzione proporzionale nel livello di emoglobina post-trasfusione al giorno (%/giorno) Endpoint secondari di sicurezza: - Eventi avversi - Reazioni trasfusionali entro 24 ore da una trasfusione di studio con il prodotto di studio assegnato - Frequenza di alloimmunizzazione agli allo-antigeni eritrocitari

E.5.2.1

Timepoint(s) of evaluation of this end point

Study participation is expected to require approximately 12 months.

La partecipazione allo studio per ogni paziente dovrebbe essere di circa 12 mesi.

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

Yes

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

Yes

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

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

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

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

Although the study ends for patients after a serum sample collection at the last visit on Day 90, the database-lock date will be used as the formal end-of-research date. Testing and data entry of test results of the last serum sample collected for the last patient is required as part of the study analysis and therefore justifies the database-lock date as the end-of-research date.

la data di chiusura del database sarà considerata come quella di termine dello studio

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

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

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

Yes

F.3.3.7.1

Details of other specific vulnerable populations

Patients with Thalassemia Major requiring chronic transfusion of RBCs

I pazienti affetti da Talassemia Major cronica che richiede una trasfusione di globuli rossi

F.4 Planned number of subjects to be included

F.4.1

In the member state

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)

The transfusion regimens required to prevent life threatening disease complications associated with these disorders will be guaranteed at the end of the study

i soggetti coinvolti nello studio, alla fine di esso, torneranno al regime trasfusionale normale

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

2012-12-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-10-16

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-05-11

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