Clinical Trials Register

Summary
EudraCT Number:	2016-004547-36
Sponsor's Protocol Code Number:	CCD-01534CA1-01
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2020-11-10
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

2016-004547-36

A.3

Full title of the trial

A RANDOMIZED, OPEN, MULTINATIONAL, MULTICENTRE, 2-PART STUDY IN SPONTANEOUSLY BREATHING PRETERM NEONATES WITH MILD TO MODERATE RESPIRATORY DISTRESS SYNDROME TO INVESTIGATE THE SAFETY, TOLERABILITY AND EFFICACY OF INHALED NEBULIZED PORACTANT ALFA (PORCINE SURFACTANT, CUROSURF®) IN COMPARISON WITH nCPAP ALONE

STUDIO RANDOMIZZATO, IN APERTO, MULTINAZIONALE, MULTICENTRICO, SUDDIVISO IN 2 PARTI NEI NEONATI PRETERMINE CON RESPIRAZIONE SPONTANEA CON SINDROME DA DISTRESS RESPIRATORIO DA LIEVE A MODERATA VOLTO A VALUTARE LA SICUREZZA, LA TOLLERABILITÀ E L’EFFICACIA DI PORACTANT ALFA (SURFATTANTE PORCINO, CUROSURF®) INALATO MEDIANTE NEBULIZZAZIONE IN CONFRONTO CON LA SOLA nCPAP

A.3.1

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

2 part study in spontaneously breathing preterm neonates with mild to moderate respiratory distress syndrome

STUDIO IN 2 PARTI NEI NEONATI PRETERMINE CON RESPIRAZIONE SPONTANEA CON SINDROME DA DISTRESS RESPIRATORIO DA LIEVE A MODERATA

A.3.2

Name or abbreviated title of the trial where available

2 part study in spontaneously breathing preterm neonates with mild to moderate respiratory distress

STUDIO IN 2 PARTI NEI NEONATI PRETERMINE CON RESPIRAZIONE SPONTANEA CON SINDROME DA DISTRESS RESPIRA

A.4.1

Sponsor's protocol code number

CCD-01534CA1-01

A.5.4

Other Identifiers

Name:

Number:

CCD-01534CA1-01

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	CHIESI FARMACEUTICI S.P.A.
B.1.3.4	Country	Italy
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	Chiesi Farmaceutici 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	Chiesi Farmaceutici S.p.A.
B.5.2	Functional name of contact point	Clinical Project manager
B.5.3	Address:
B.5.3.1	Street Address	largo Francesco Belloli 11/A
B.5.3.2	Town/ city	Parma
B.5.3.3	Post code	43122
B.5.3.4	Country	Italy
B.5.4	Telephone number	00390521279817
B.5.5	Fax number	0000000
B.5.6	E-mail	clinicaltrials_info@chiesi.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	CUROSURF
D.2.1.1.2	Name of the Marketing Authorisation holder	CHIESI Limited
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	CUROSURF
D.3.2	Product code	N/A
D.3.4	Pharmaceutical form	Nebuliser suspension
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PORACTANT ALFA
D.3.9.1	CAS number	129069-19-8
D.3.9.2	Current sponsor code	na
D.3.9.4	EV Substance Code	SUB22150
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	80
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	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	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	Yes
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

Mild to moderate respiratory distress syndrome

SINDROME DA DISTRESS RESPIRATORIO DA LIEVE A MODERATA

E.1.1.1

Medical condition in easily understood language

respiratory distress syndrome

SINDROME DA DISTRESS RESPIRATORIO

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10038690
E.1.2	Term	Respiratory distress syndrome (neonatal)
E.1.2	System Organ Class	100000004855

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Part I: Objective
To assess the safety and tolerability of three single ascending doses of nebulized Curosurf¿.

Part II Objective
To compare the efficacy of nebulized Curosurf¿, administered at low dose (dose 1) or high dose (dose 2), during nCPAP, versus nCPAP alone in terms of incidence of respiratory failure in the first 72 hours of life in spontaneously breathing preterm neonates with mild to moderate RDS.

Parte I
Valutare la sicurezza e la tollerabilit¿ di tre dosi singole crescenti di Curosurf¿ nebulizzato.
Parte II
Confrontare l¿efficacia di Curosurf¿ nebulizzato, somministrato a dose bassa (dose 1) o alta (dose 2), durante la nCPAP, rispetto alla nCPAP in monoterapia in termini di incidenza di insufficienza respiratoria nelle prime 72 ore di vita in neonati pretermine che respirano spontaneamente affetti da RDS da lieve a moderata.

E.2.2

Secondary objectives of the trial

Not applicable

Non applicabile

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Neonates must meet all of the following inclusion criteria to be eligible for enrolment into the study:
1. Written informed consent obtained by parents/legal representative (according to local regulation) prior to or after birth.
2. Inborn neonates from 28+0 to 32+6 weeks of GA, spontaneously breathing and stabilized on nCPAP within 1 hour from birth. In each dose group, neonates with GA from 28+0 to 32+6 will be enrolled first.
3. Clinical course consistent with RDS.
4. Receiving CPAP pressure 5-8 cm H2O and FiO2 between 0.25 and 0.40 to maintain SpO2 between 88% and 95% for at least 30 minutes between 60 minutes and 12 hours after birth.

I neonati devono soddisfare tutti i seguenti criteri di inclusione per risultare idonei all’arruolamento nello studio:
1. Consenso informato scritto ottenuto dai genitori/dal rappresentante legale (in conformità alla normativa locale) prima o dopo la nascita.
2. Bambini nati presso il centro dopo 28+0-32+6 settimane di EG, in grado di respirare spontaneamente e stabilizzati con nCPAP entro un’ora dalla nascita.
In ciascun gruppo di dose, saranno arruolati per primi i neonati con EG da 28+0 a 32+6 settimane.
3. Decorso clinico coerente con l’RDS.
4. Trattamento con CPAP a pressione di 5-8 cm H2O e frazione di ossigeno inspirato (FiO2) tra 0,25 e 0,40 per mantenere la saturazione periferica di ossigeno determinata mediante pulsossimetria (SpO2) tra 88% e 95% per almeno 30 minuti a distanza di 60 minuti-12 ore dal parto.

E.4

Principal exclusion criteria

The presence of any of the following will exclude a neonate from study enrolment:
1. Early need for endotracheal intubation for cardiopulmonary resuscitation in delivery room or within 1 hour from birth because of severe RDS [one of the following conditions: rapid (i.e. within 1 h) and persistent (> 30 min) escalation of FiO2 > 0.40 for target SpO2 88-95% in 1 hour, recurrent episodes of apnoea (>2 episodes) requiring positive pressure ventilation (PPV)].
2. Respiratory distress not secondary to surfactant deficiency (see APPENDIX 3).
3. Use of surfactant prior to study entry and need for endotracheal administration of any other treatment.
4. Evidence of severe birth asphyxia (e.g. Apgar score <= 5 at 10 minutes after birth, or continued need for resuscitation at 10 minutes after birth, altered neurological state or neonatal encephalopathy).
5. Major congenital anomalies.
6. Mothers with prolonged rupture of the membranes (> 21 days duration) which could cause complications (in particular severe pulmonary hypoplasia due to oligohydramnios).
7. Presence of air leaks identified and known prior to study entry.
8. Presence of IVH >= III identified and known prior to study entry.
9. Hypotension or evidence of hemodynamic instability requiring pharmacological intervention for hemodynamic support.
10. Any condition that, in the opinion of the Investigator, would place the neonate at undue risk.
11. Participation in another clinical trial of any placebo, experimental medical device or biological substance conducted under the provisions of a protocol on the same therapeutic target; the participation in studies involving diagnostic devices or studies with treatments for different conditions than lung and respiratory function impairments s may be permitted following an agreement with the sponsor. Non interventional observational studies are allowed.

La presenza di uno qualsiasi dei seguenti elementi escluderà il neonato dall’arruolamento nello studio:
1. Necessità precoce di intubazione endotracheale per la rianimazione cardiopolmonare in sala parto o entro 1 ora dalla nascita a causa di RDS grave (una delle seguenti condizioni: aumento rapido [ovvero, entro 1 ora] e persistente [>30 minuti] della FiO2 >0,40 per la SpO2 target di 88-95% in 1 ora, episodi ricorrenti di apnea [>2 episodi] che richiedono ventilazione a pressione positiva [PPV]).
2. Distress respiratorio non secondario al deficit di surfattante (vedere APPENDICE 3).
3. Uso di surfattanti prima dell’ingresso nello studio e necessità di somministrazione endotracheale di qualsiasi altro trattamento.
4. Evidenza di grave asfissia alla nascita (ad es., punteggio Apgar <=5 a 10 minuti dalla nascita o necessità continua di rianimazione a 10 minuti dalla nascita, oppure stato neurologico alterato o encefalopatia neonatale).
5. Anomalie congenite maggiori.
6. Madri con rottura prematura prolungata delle membrane (>21 giorni di durata) che potrebbe provocare complicazioni (in particolare, grave ipoplasia polmonare dovuta a oligoidramnios).
7. Presenza di perdite d’aria identificate e note prima dell’ingresso nello studio.
8. Presenza di emorragia intraventricolare (IVH) di grado >=III identificata e nota prima dell’ingresso nello studio.
9. Ipotensione o evidenza di instabilità emodinamica che richiede l’intervento farmacologico per fornire supporto emodinamico.
10. Qualsiasi condizione che, a giudizio dello Sperimentatore, comporterebbe un rischio ingiustificato per il neonato.
11. Partecipazione a un’altra sperimentazione clinica inerente un qualsiasi placebo, dispositivo medico sperimentale o sostanza biologica e condotta secondo le disposizioni di un protocollo sullo stesso target terapeutico; la partecipazione a studi che prevedono l’uso di dispositivi diagnostici o a studi con trattamenti per condizioni diverse da insufficienze della funzione polmonare e respiratoria potrebbe essere consentita a seguito di accordi preventivi con lo sponsor. È consentita la partecipazione a studi osservazionali non interventistici.

E.5 End points

E.5.1

Primary end point(s)

Safety parameters (AEs and ADRs) and Respiratory failure (needing additional poractant ET administration or mecanical ventilation)

Parametri di sicurezza (AEs e ADRs) e insufficienza respiratoria (che necessitano di ulteriore somministrazione di poractant ET o ventilazione meccanica)

E.5.1.1

Timepoint(s) of evaluation of this end point

during 72 h of life and up to diagnosis of BPD

durante 72 ore di vita e fino alla diagnosi di BPD

E.5.2

Secondary end point(s)

Blood gas analysis and measure of SpO2

Emogasanalisi e misura di SpO2

E.5.2.1

Timepoint(s) of evaluation of this end point

During 72 h of life and up to diagnosis of BPD

durante 72 ore di vita e fino alla diagnosi di BPD

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

Yes

E.6.13.1

Other scope of the trial description

Tolerability

Tollerabilit¿

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

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

Yes

E.8.1.7.1

Other trial design description

Studio in due parti

This is 2 part study

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

nCPAP

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

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

The end of the trial will correspond to the date of the assessment for BPD diagnosis based on GA (discharge home or 36 weeks PMA or between 28 days and 56 days PNA) of the last baby of Part II from the recruiting site or from the continuing care site in case the treated baby was transferred from
the original recruiting site.

La fine della sperimentazione corrisponderà alla data della valutazione per la diagnosi di BPD basata su GA (dimissione domiciliare o PMA di 36 settimane o tra 28 e 56 giorni PNA) dell'ultimo bambino della Parte II dal sito di reclutamento o dal sito di proseguimento della cura nel caso in cui il bambino trattato è stato trasferito dal sito di reclutamento originale.

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.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

Yes

F.1.1.2.1

Number of subjects for this age range:

288

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)

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

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

288

F.4.2.2

In the whole clinical trial

288

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

2017-07-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-04-11

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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