Clinical Trials Register

Summary
EudraCT Number:	2015-001344-11
Sponsor's Protocol Code Number:	CCD-GPLSCD01-03-FU
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:	2020-09-29
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

2015-001344-11

A.3

Full title of the trial

Multinational, multicenter, prospective, long-term safety and efficacy follow-up study after Autologous Cultivated Limbal Stem Cells Transplantation (ACLSCT) for restoration of corneal epithelium in patients with limbal stem cell deficiency due to ocular burns (HOLOCORE-FU)

Studio di controllo (follow up) multinazionale, multicentrico, prospettico, di efficacia e di sicurezza a lungo termine dopo trapianto di cellule staminali limbari autologhe coltivate (ACLSCT) finalizzato al ripristino dell’epitelio corneale in pazienti con deficit di cellule staminali limbari dovuto ad ustioni oculari (HOLOCORE-FU)

A.3.1

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

A clinical study to follow up the implantation of Holoclar on the cornea of patients with ocular burns

Studio clinico per seguire l'impianto di Holoclar sulla cornea di pazienti con ustioni oculari

A.3.2

Name or abbreviated title of the trial where available

HOLOCORE FU

A.4.1

Sponsor's protocol code number

CCD-GPLSCD01-03-FU

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/199/2012

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 SpA
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 Spa
B.5.2	Functional name of contact point	Clinical Project Manager
B.5.3	Address:
B.5.3.1	Street Address	via Palermo 26A
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	003905211689281
B.5.5	Fax number	00390521774468
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	HOLOCLAR
D.2.1.1.2	Name of the Marketing Authorisation holder	Chiesi Farmaceutici S.p.A.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/08/579
D.3 Description of the IMP
D.3.1	Product name	Holoclar
D.3.2	Product code	[Holoclar]
D.3.4	Pharmaceutical form	Implant
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Ophthalmic use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Ex vivo autologous corneal epithelial cells including stem cells
D.3.9.2	Current sponsor code	GPLSCD01
D.3.9.4	EV Substance Code	SUB172912
D.3.10	Strength
D.3.10.1	Concentration unit	cm2 square centimeter
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	4
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)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Yes
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	Yes
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	Yes
D.3.11.3.5.1	CAT classification and reference number	Tissue Engineered Product (EMA/54465/2011)
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	ATIMP

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

corneal lesions with associated moderate to severe limbal stem cell deficiency due to ocular burns

Lesioni corneali con associato deficit di cellule staminali limbari da moderato a grave dovuto a ustioni oculari

E.1.1.1

Medical condition in easily understood language

corneal damage due to ocular burns

Danneggiamento corneale dovuto a ustioni oculari

E.1.1.2

Therapeutic area

Diseases [C] - Eye Diseases [C11]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10011012
E.1.2	Term	Corneal epithelium opacity
E.1.2	System Organ Class	100000004853

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 demonstrate the long term safety of one or two implants with Holoclar in patients suffering from moderate to severe LSCD secondary to ocular burns.

Dimostrare la sicurezza a lungo termine di uno o due ACLSCT con Holoclar in pazienti affetti da LSCD da moderato a grave in seguito ad ustioni oculari.

E.2.2

Secondary objectives of the trial

1)To evaluate the long-term efficacy of one or two ACLSCT(s), the degree of superficial corneal neo-vascularization and corneal epithelial stability, clinical symptoms, conjunctival inflammation, visual acuity, quality of life, tear secretion compared to baseline (i.e. before the first ACLSCT) and long term efficacy based on clinical judgment of the investigator;
2) To evaluate safety and clinical outcomes (i.e. superficial corneal neo-vascularization, epithelial defects, visual acuity, conjunctival inflammation, and symptoms) after keratoplasty
in patients previously treated with Holoclar.

1) Valutare l'efficacia a lungo termine di uno o due ACLSCT, il grado di neo-vascolarizzazione corneale superficiale e la stabilità epiteliale corneale, i sintomi clinici, l’infiammazione congiuntivale, l’acuità visiva, la qualità di vita, la secrezione lacrimale rispetto alla baseline (cioè antecedente al primo ACLSCT) ed l’efficacia a lungo termine secondo il giudizio clinico dello sperimentatore;
2) Valutare gli esiti clinici e di sicurezza (cioè neo-vascolarizzazione corneale superficiale, difetti epiteliali, acuità visiva, infiammazione congiuntivale e sintomi) dopo cheratoplastica nei pazienti sottoposti in precedenza a trattamento con Holoclar.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

All patients (adults and pediatrics) who completed the HOLOCORE core study and who consent to roll over to the present extension study at the end of the HOLOCORE follow-up.

Tutti i pazienti (adulti e pediatrici) che hanno completato lo studio principale HOLOCORE e che acconsentonoall'arruolamento in questo studio di estensione al termine del controllo di HOLOCORE.

E.4

Principal exclusion criteria

No specific exclusion criterion is considered for this study, except for patients dropping out from the HOLOCORE study or withdrawing
consent.

Non si considerano criteri di esclusione specifici in questo studio, fatto salvo laddove i pazienti abbandonino lo studio HOLOCORE o ritirino il consenso.

E.5 End points

E.5.1

Primary end point(s)

Percentage of patients reporting Treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), Adverse Event of Special Interest in accordance with the Risk Management Plan for Holoclar (AESI), including glaucoma and blepharitis.

Percentuale di pazienti che riportano eventi avversi emersi durante il trattamento (TEAE), eventi avversi correlate al trattamento (TRAE), eventi avversi di speciale interesse (AESI), inclusi glaucoma e blefarite, in accordo con il Piano di Gestione del Rischio di Holoclar.

E.5.1.1

Timepoint(s) of evaluation of this end point

All study duration

Per tutta la durata dello studio

E.5.2

Secondary end point(s)

Percentage of patients with successful transplantation at Visit 3 (success is defined on the basis of the degree of "superficial corneal neovascularization" and "epithelial defects")

Percentuale di pazienti con trapianto riuscito a Visit 3 (il successo è definito sulla base del grado di "neovascolarizzazione corneale superificiale" e "difetti epiteliali")

E.5.2.1

Timepoint(s) of evaluation of this end point

12 months after patient inclusion

12 mesi dopo l'inclusione del paziente nello studio

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

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

Follow up dei pazienti che hanno ricevuto HOLOCLAR nel protocollo HOLOCORE.

Follow up of patients who received HOLOCLAR in HOLOCORE protocol.

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

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

Yes

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)

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 2020-09-29.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

Yes

F.3.3.4

Nursing women

Yes

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Minor patients

Pazienti minorenni

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

2017-06-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-06-08

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

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