Clinical Trials Register

Summary
EudraCT Number:	2020-005263-31
Sponsor's Protocol Code Number:	LEVOKETO_02-2020
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2021-02-09
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

2020-005263-31

A.3

Full title of the trial

Assessment of the effects and tolerability of RD03/2016 (Levofloxacin; Ketorolac Trometamol 0.5+0.5% w/v eye drops solution) for the treatment of bacterial conjunctivitis in adults: a multicentre, randomized, blinded-assessor, phase II non inferiority study – MIRAKLE

Eficacia y tolerabilidad de RD03/2016 (solución oftálmica de levofloxacino; ketorolaco trometamol 0,5+0,5% m/v) para el tratamiento de la conjuntivitis bacteriana en adultos: estudio clínico en fase II de no inferioridad, multicéntrico, aleatorizado, enmascarado para el evaluador. Estudio MIRAKLE.

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

MIRAKLE

A.4.1

Sponsor's protocol code number

LEVOKETO_02-2020

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	NTC SRL
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	NTC s.r.l
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	OPIS s.r.l.
B.5.2	Functional name of contact point	Medical Department
B.5.3	Address:
B.5.3.1	Street Address	Via Matteotti, 10
B.5.3.2	Town/ city	Desio (MB)
B.5.3.3	Post code	20832
B.5.3.4	Country	Italy
B.5.4	Telephone number	003903626331
B.5.5	Fax number	00390039633633
B.5.6	E-mail	info.studiclinici@opis.it

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	RD03/2016
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	Ocular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LEVOFLOXACIN
D.3.9.1	CAS number	100986-85-4
D.3.9.4	EV Substance Code	SUB08471MIG
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	5
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	KETOROLAC TROMETAMOL
D.3.9.1	CAS number	74103-07-4
D.3.9.4	EV Substance Code	SUB02835MIG
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	5
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.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	OFTAQUIX - 1 FLACONE DI COLLIRO 0.5% DA 5 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	Santen OY
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	Oftaquix
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	Ocular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LEVOFLOXACIN
D.3.9.1	CAS number	100986-85-4
D.3.9.4	EV Substance Code	SUB08471MIG
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	5
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

Bacterial conjunctivitis

Conjuntivitis bacteriana

E.1.1.1

Medical condition in easily understood language

Bacterial conjunctivitis

Conjuntivitis bacteriana

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	PT
E.1.2	Classification code	10061784
E.1.2	Term	Conjunctivitis bacterial
E.1.2	System Organ Class	10021881 - Infections and infestations

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 demonstrate the non-inferiority of RD03/2016 eye drops vs. levofloxacin alone in microbiological eradication at final visit (Day 7-9)

Demostrar la no inferioridad del colirio RD03/2016 frente al levofloxacino solo en colirio, en la erradicación microbiológica en la visita final (día 7-9).

E.2.2

Secondary objectives of the trial

-To assess the efficacy of RD03/2016 eye drops vs. levofloxacin alone in the
proportion of patients with clinical cure, i.e. resolution of cardinal signs of
bacterial conjunctivitis, at On-Therapy (OT) visit (Day 3-4) and final visit (Day 7-
9).
-To assess the efficacy of RD03/2016 eye drops vs. levofloxacin alone in time to
clinical cure, assessed through photographs taken every 12 ± 1 hours from Day 1 to Day
7-9, using eyePRO.net (photographs on Day 0 to be taken at the earliest feasible time
point post-baseline visit)
- To assess the efficacy of RD03/2016 eye drops vs. levofloxacin alone in time to
resolution of symptoms of bacterial conjunctivitis.
- To evaluate the safety and tolerability of RD03/2016 eye drops
- To evaluate compliance with the prescribed treatment
For other secondary objectives see the protocol.

- Evaluar la eficacia del colirio RD03/2016 frente a levofloxacino solo en colirio, en la proporción de pacientes con curación clínica (resolución de los signos principales) de la conjuntivitis bacteriana, en la visita durante el tratamiento (en inglés on-therapy, OT) (día 3-4) y en la visita final (día 7-9).
- Evaluar la eficacia del colirio RD03/2016 frente al levofloxacino solo en colirio, durante el tiempo transcurrido hasta la curación clínica, determinado mediante fotografías tomadas cada 12 ± 1 horas, desde el día 0 hasta el día 7-9, utilizando eyePROD.net (fotos del día 0 a tomar inmediatamente después de la visita basal).
- Evaluar la eficacia del colirio RD03/2016 frente al levofloxacino solo en colirio, durante el tiempo transcurrido hasta la resolución de los síntomas de conjuntivitis bacteriana.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Ability of patient to consent and provide signed written informed consent
2. Male or female aged major/= 18 year
3. Clinical diagnosis of acute bacterial conjunctivitis with moderate/severe signs
(score = 2 for each cardinal signs, i.e. bulbar conjunctival injection, palpebral
conjunctival injection and conjunctival discharge, in at least one eye), not previously treated with antibiotics, steroids and nonsteroidal anti-inflammatory drugs (NSAIDs)
4. Able and willing to follow study procedures
5. Availability of a person (a relative or a caregiver) to be trained for the execution of the photographic documentation required by the study and for the use of eyePRO.net (see Study procedures)
6. Willing to interrupt the use of contact lenses for the entire duration of the study

1. Capacidad del paciente para dar su consentimiento y obtención del consentimiento informado por escrito y firmado.
2. Pacientes de sexo masculino y femenino, de edad ≥ 18 años.
3. Diagnóstico clínico de conjuntivitis bacteriana aguda con signos moderados/intensos (puntuación ≥ 2 para cada signo principal, es decir, congestión sanguínea de la conjuntiva ocular, congestión sanguínea de la conjuntiva palpebral y secreción conjuntival, al menos en un ojo), no tratados anteriormente con antibióticos, corticoesteroides o fármacos antiinflamatorios no esteroideos (AINE).
4. Pacientes dispuestos y capaces de seguir los procedimientos del estudio.
5. Disponibilidad de una persona (un familiar, conocido o asistente) a recibir formación sobre la preparación de la documentación fotográfica exigida por el estudio y el uso de eyePRO.net (véase los procedimientos del estudio).
6. Pacientes dispuestos a dejar de utilizar las lentes de contacto mientras dure el estudio.

E.4

Principal exclusion criteria

1. Any acute ocular disease other than bacterial conjunctivitis
2. Any ocular surgery (including laser treatment) in the study eye within 30 days prior to study entry
3. Any ocular (in the study eye) or systemic antimicrobial agents administered concurrently or within 3 days prior to study entry
4. Any ocular (in the study eye) or systemic steroids or NSAIDs administered concurrently
5. Pathological conditions or treatments that in the opinion of the Investigator may interfere with the efficacy and/or safety evaluations of the study (e.g. chronic blepharitis, glaucoma, moderate-severe dry eye)
6. Participation in previous clinical studies if less than 5 half-lives of the
Investigational Medicinal Product (IMP) used have passed
7. Hypersensitivity to the products, other quinolones, acetylsalicylic acid and other NSAIDs (due to potential for cross-sensitivity), or their excipients
8. Contraindications to ocular treatment with levofloxacin and/or ketorolac
9. Pregnancy or breastfeeding

1. Cualquier patología ocular aguda distinta de la conjuntivitis bacteriana.
2. Cualquier intervención quirúrgica ocular en el ojo en estudio (incluida la laserterapia) en los 30 días anteriores a la inclusión en el estudio.
3. Cualquier antibiótico suministrado por vía ocular (en el ojo en estudio) o sistémica de forma concomitante o en los 3 días anteriores a la inclusión en el estudio.
4. Cualquier corticoesteroide o AINE suministrado de forma concomitante por vía ocular (en el ojo en estudio) o sistémica.
5. Patologías o tratamientos que, en opinión del investigador, puedan interferir en las evaluaciones de la eficacia y/o la seguridad del estudio (p. ej. blefaritis crónica, glaucoma, xeroftalmía moderada o intensa).
6. Participación en anteriores estudios clínicos si han transcurrido menos de 5 semividas del producto en investigación (PEI).
7. Hipersensibilidad a los productos en estudio, otras quinolonas, ácido acetilsalicílico y otros AINE (dado el potencial de sensibilidad cruzada) o a cualquiera de sus excipientes.
8. Contraindicaciones al tratamiento ocular con levofloxacino y/o ketorolaco.
9. Embarazo o lactancia.

E.5 End points

E.5.1

Primary end point(s)

- Proportion of patients with microbiological eradication i.e. absence/no growth of
baseline pathogens assessed through bacteriological culture (calcium alginate swab of the lower conjunctiva) at final visit (Day 7-9);

Proporción de pacientes con erradicación microbiológica, es decir, ausencia/ningún crecimiento de los patógenos presentes en la visita basal, evaluado mediante cultivo bacteriológico (extracción de una muestra con hisopo de alginato de calcio a nivel de la conjuntiva inferior) en la visita final (día 7-9).

E.5.1.1

Timepoint(s) of evaluation of this end point

Days 7-9

Días 7-9

E.5.2

Secondary end point(s)

-Proportion of patients with clinical cure, i.e. absence of cardinal signs of bacterial conjunctivitis (conjunctival discharge, bulbar conjunctival injectionand
palpebral conjunctival injection) at OT visit (Day 3-4) and final visit (Day 7-9);
-Time to clinical cure assessed through photographs taken every 12 ± 1 hours from Day 1 to Day 7-9, using the study smartphone and eyePRO.net;
- Time to resolution (absence) of bacterial conjunctivitis symptoms (pain,
burning/stinging, itching, tearing, foreign body sensation, photophobia and
discomfort) recorded by the patient (0, absent; 1, present) every 12 ± 1 hours from Day 1 to Day 7-9 through an electronic patient diary;

- Proporción de pacientes con curación clínica, es decir, con resolución de los signos principales de conjuntivitis bacteriana (secreción conjuntival, congestión sanguínea o hiperemia de la conjuntiva ocular y congestión sanguínea de la conjuntiva palpebral), en la visita OT (día 3-4) y en la visita final (día 7-9).
- Tiempo transcurrido hasta la curación clínica, determinado mediante fotografías tomadas cada 12 ± 1 horas, desde el día 0 hasta el día 7-9, utilizando el smartphone del estudio facilitado al paciente y eyePROD.net. Cabe destacar que, el día 0, las fotografías deberán tomarse inmediatamente después de la visita basal.
- Tiempo transcurrido hasta la resolución (ausencia) de los síntomas de conjuntivitis bacteriana (dolor, quemazón/escozor, prurito, lagrimeo, sensación de cuerpo extraño, fotofobia y molestia) registrados por el paciente (0, ausente; 1, presente) cada 12 ± 1 horas, desde el día 0 hasta el día 7-9, a través del diario electrónico. Cabe destacar que, el día 0, los síntomas deberán registrarse inmediatamente después de la visita basal.

E.5.2.1

Timepoint(s) of evaluation of this end point

Days 7-9

Días 7-9

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

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)

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

E.8.1.3

Single blind

Yes

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

Enmascarado para el evaluador

Blinded-assessor

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

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Russian Federation

Germany

Italy

Portugal

Spain

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

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 months

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:

126

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

126

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

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

200

F.4.2.2

In the whole clinical trial

252

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)

standard therapy

Terapia estándar

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

2021-06-02

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-02-26

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

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