Clinical Trials Register

Summary
EudraCT Number:	2022-001662-35
Sponsor's Protocol Code Number:	BTIIMD-02-EC/22/GLAUCOMA
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-06-07
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2022-001662-35

A.3

Full title of the trial

Randomized, double-blind, parallel group clinical trial to evaluate the efficacy and safety of PRGF eye drops as a treatment for dry eye disease in patients with glaucoma

Ensayo clínico aleatorizado, de grupos paralelos doble ciego para evaluar la eficacia y la seguridad del colirio de PRGF como tratamiento de la enfermedad del ojo seco en pacientes con glaucoma

A.3.1

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

Clinical trial to evaluate the efficacy and safety of PRGF eye drops as a treatment for dry eye disease in patients with glaucoma

Ensayo clínico para evaluar la eficacia y la seguridad del colirio de PRGF como tratamiento de la enfermedad del ojo seco en pacientes con glaucoma

A.4.1

Sponsor's protocol code number

BTIIMD-02-EC/22/GLAUCOMA

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	BTI I MAS D S.L.
B.1.3.4	Country	Spain
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	BTI I MAS D
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	BTI I MAS D
B.5.2	Functional name of contact point	Clinical Trials Unit
B.5.3	Address:
B.5.3.1	Street Address	Jacinto Quincoces 39
B.5.3.2	Town/ city	Vitoria
B.5.3.3	Post code	01007
B.5.3.4	Country	Spain
B.5.6	E-mail	mikel.allende@bti-implant.es

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	PRGF
D.3.4	Pharmaceutical form	Eye drops, solution
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	PRGF
D.3.9.3	Other descriptive name	PLATELET CONCENTRATE
D.3.9.4	EV Substance Code	SUB14918MIG
D.3.10	Strength
D.3.10.1	Concentration unit	U unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
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	Yes
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	Yes
D.2.1.1.1	Trade name	Laboratorios Théa
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Hyabak
D.3.4	Pharmaceutical form	Eye drops, solution
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	Hyabak
D.3.9.1	CAS number	9004-61-9
D.3.9.3	Other descriptive name	HYALURONIC ACID
D.3.9.4	EV Substance Code	SUB14126MIG
D.3.10	Strength
D.3.10.1	Concentration unit	ml millilitre(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
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	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	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

Dry eye disease in patients with glaucoma

Enfermedad de ojo seco en pacientes con glaucoma

E.1.1.1

Medical condition in easily understood language

Dry eye disease in patients with glaucoma

Enfermedad de ojo seco en pacientes con glaucoma

E.1.1.2

Therapeutic area

Diseases [C] - Eye Diseases [C11]

MedDRA Classification

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 evaluate the efficacy of PRGF® eye drops to relieve dry eye symptoms in patients with glaucoma.

Evaluar la eficacia del colirio de PRGF® para aliviar la sintomatología del ojo seco en pacientes con glaucoma.

E.2.2

Secondary objectives of the trial

To determine the safety profile of PRGF eye drops in the treatment of dry eye disease in patients with glaucoma.

Determinar el perfil de seguridad del colirio de PRGF en el tratamiento de la enfermedad del ojo seco en pacientes con glaucoma.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Inclusion criteria
1. Signed and dated informed consent.
2. Male or female between 50-80 years of age.
3. Controlled glaucoma or ocular hypertension (OHT) that require pharmacological treatment with at least one active ingredient with preservatives and present dry eyes.
4. The patient must have stopped treatment with artificial tears at least one week before this visit
5. Diagnosis of moderate to severe dry eye syndrome defined by OSDI score ≥ 13
6. Patient who has at least one eye that meets the following requirements:
• Total ocular staining (cornea and conjunctiva) with Oxford scale of grade between grade 2 to 5
• At least one of the following objective signs:
o Schirmer test ≥ 3 mm/5 min and ≤ 9 mm/5 min,
o TBUT: <10 seconds.
7. Patients with glaucoma: involvement of the optic nerve compatible with this disease (focal or diffuse thinning of the neuroretinal ring), observed by previous optical coherence tomography (OCT), regardless of whether they have a campimetric defect or IOP level.
8. Patients with OHT: IOP > 21 mmHg in at least two measurements, without optic nerve involvement, requiring ocular hypotensive treatment
9. Absence of progression of OHT or glaucoma in the year prior to the start of the study, objectified by OCT and/or campimetry.

1. Consentimiento informado firmado y fechado.
2. Hombre o mujer entre 50-80 años de edad.
3. Glaucoma o hipertensión ocular (HTO) controlados que requieran tratamiento farmacológico con, al menos, un principio activo con conservantes y presenten sequedad ocular.
4. El paciente debe de haber suspendido el tratamiento con lágrimas artificiales al menos una semana antes de esta visita
5. Diagnóstico del síndrome del ojo seco de moderado a severo definido por la puntuación del OSDI ≥ 13
6. Paciente que tiene al menos un ojo que cumple con los requisitos siguientes:
• Tinción ocular total (cornea y conjuntiva) con escala de Oxford de grado entre grado 2 a 5
• Al menos uno de los siguientes signos objetivos:
o Prueba de Schirmer ≥ 3 mm/5 min y ≤ 9 mm/5 min,
o TBUT: <10 segundos.
7. Pacientes con glaucoma: afectación del nervio óptico compatible con esta enfermedad (adelgazamiento focal o difuso del anillo neurorretiniano), objetivado por tomografía óptica de coherencia (OCT) previa, independiente de que tengan defecto campimétrico y de la cifra de PIO.
8. Pacientes con HTO: PIO > 21 mmHg en al menos dos mediciones, sin afectación del nervio óptico, que precise tratamiento hipotensor ocular
9. Ausencia de progresión de la HTO o glaucoma en el año previo al inicio del estudio, objetivable mediante OCT y/o campimetría.

E.4

Principal exclusion criteria

1. Ocular rosacea
2. History of ocular trauma or ocular infection in the previous 3 months
3. History of ocular allergy
4. History of uveitis (last episode less than 6 months)
5. History of inflammatory corneal ulcer in the last 12 months
6. Ocular surgery in the previous 3 months or foreseen indication of ocular surgery during the duration of the study
Systemic/non-ophthalmic exclusion criteria
7. Known or suspected hypersensitivity to one of the components of the investigational product or ancillary products
8. History of any active systemic condition incompatible with the investigation or that, in the opinion of the investigator, may interfere with the results of the investigation or with the safety of the patient
9. Active allergic rhinitis or susceptible to reactivation during the investigation
10. Any other medical or surgical history, disorder or disease likely to require or modify systemic medication during the investigation (systemic medication must be stable in the three months prior to screening).
11. Pregnancy or breastfeeding
12. Women of childbearing age who are not using reliable contraceptive methods (oral contraceptives, IUDs, subdermal contraceptive implants, vaginal ring, patch) and who have not undergone surgical sterilization.
13. Inability of the patient to understand the research procedures or to give informed consent.
14. Non-compliance by the patient (eg, refusal to attend a visit or to complete a questionnaire or study tests);
15. Participation in this essay at the same time as in another.
16. Participation in this trial during the exclusion period of another trial
17. Patients who are hospitalized by judicial or regulatory order, who are admitted to psychiatric centers, penitentiary or state institutions, and employees of research centers or the company of the promoter
18. Patient not covered by the public health system
19. Patient under guardianship or under judicial guardianship
20. Patients who have used or are using a prohibited treatment (or make a prohibited modification of the therapeutic regimen).

1. Rosácea ocular
2. Antecedentes de trauma ocular o infección ocular en los 3 meses previos
3. Antecedentes de alergia ocular
4. Antecedentes de uveítis (último episodio menor a 6 meses)
5. Antecedentes de úlcera corneal inflamatoria en los últimos 12 meses
6. Cirugía ocular en los 3 meses previos o previsión de indicación de cirugía ocular durante el periodo de duración del estudio
Criterios de exclusión de carácter sistémico/no oftálmico
7. Hipersensibilidad conocida o presumible a uno de los componentes del producto en investigación o los productos auxiliares
8. Antecedentes de cualquier afección sistémica activa incompatible con la investigación o que, según el criterio del investigador, pueda interferir con los resultados de la investigación o con la seguridad del paciente
9. Rinitis alérgica activa o susceptible de reactivarse durante la investigación
10. Cualquier otro antecedente médico o quirúrgico, trastorno o enfermedad susceptible de requerir o modificar la medicación sistémica durante la investigación (la medicación sistémica debe ser estable en los tres meses anteriores a la selección).
11. Embarazo o lactancia materna
12. Mujeres en edad fértil que no utilicen métodos anticonceptivos fiables (anticonceptivos orales, DIU, implantes anticonceptivos subdérmicos, anillo vaginal, parche) y que no hayan sido objeto de esterilización quirúrgica.
13. Incapacidad del paciente para comprender los procedimientos de la investigación o para otorgar su consentimiento informado.
14. Incumplimiento por parte de la paciente (p.ej; negarse a acudir a una visita o a cumplimentar cuestionario o pruebas del estudio);
15. Participación en este ensayo a la vez que lo hace en otro.
16. Participación en este ensayo durante el periodo de exclusión de otro ensayo
17. Pacientes que estén internados por orden judicial o reguladora, que estén ingresados en centros psiquiátricos, en instituciones penitenciarias o estatales, y los empleados de los centros de investigación o de la empresa del promotor
18. Paciente no cubierto por el sistema de salud público
19. Paciente bajo tutela o bajo tutela judicial
20. Pacientes que hayan utilizado o utilicen un tratamiento prohibido (o realizar una modificación prohibida del régimen terapéutico).

E.5 End points

E.5.1

Primary end point(s)

- Change in the degree of ocular staining at 6 months using the Oxford scale.
- Evolution of symptoms at 6 months according to the Ocular Surface Disease Index (OSDI).

- Cambio en el grado de tinción ocular a los 6 meses empleando la escala de Oxford.
- Evolución de la sintomatología a los 6 meses según el Índice de Enfermedades en la Superficie Ocular (OSDI).

E.5.1.1

Timepoint(s) of evaluation of this end point

6 months

6 meses

E.5.2

Secondary end point(s)

- Change in the degree of ocular staining at 3 months using the Oxford scale.
- Evolution of symptoms at 3 months according to the Ocular Surface Disease Index (OSDI).
- Change in the amount of tears produced at 3 and 6 months using the Schirmer test.
- Change in tear break-up time (TBUT) at 3 and 6 months
- Evolution of conjunctival hyperemia at 3 and 6 months using the McMonnies photographic scale.
- Evolution of corrected distance visual acuity in both eyes at 3 and 6 months.
- Assessment of ocular symptoms in the previous 48 hours through a clinical questionnaire.
- Change in the concentration of the inflammation biomarker S100A8 in tears at 3 and 6 months post-treatment.
- Overall tolerance assessed by the investigator at 3 and 6 months.
- Global tolerance assessed by the patient at 3 and 6 months.
- Type and frequency of ocular adverse events.
- Type and frequency of systemic adverse events.

- Cambio en el grado de tinción ocular a los 3 meses empleando la escala de Oxford.
- Evolución de la sintomatología a los 3 meses según el Índice de Enfermedades en la Superficie Ocular (OSDI).
- Cambio en la cantidad de lágrima producida a los 3 y 6 meses empleando la Prueba de Schirmer.
- Cambio en el tiempo de ruptura lagrimal (TBUT) a los 3 y 6 meses
- Evolución de la hiperemia conjuntival a los 3 y 6 meses utilizando la escala fotográfica de McMonnies.
- Evolución de la agudeza visual corregida de lejos en ambos ojos a los 3 y 6 meses.
- Valoración de los síntomas oculares en las 48 horas previas a través de cuestionario clínico.
- Cambio en la concentración del biomarcador de inflamación S100A8 en lágrima a los 3 y 6 meses post-tratamiento.
- Tolerancia global evaluada por el investigador a los 3 y 6 meses.
- Tolerancia global evaluada por el paciente a los 3 y 6 meses.
- Tipo y frecuencia de acontecimientos adversos oculares.
- Tipo y frecuencia de acontecimientos adversos sistémicos.

E.5.2.1

Timepoint(s) of evaluation of this end point

3 and 6 months

3 y 6 meses

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)

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

Yes

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)

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

Yes

E.8.4

The trial involves multiple sites in the 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

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

LVLP

UVUP

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)

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)

None

Ninguno

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

2022-08-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-07-28

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials