Clinical Trials Register

Summary
EudraCT Number:	2017-002835-40
Sponsor's Protocol Code Number:	AK701
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:	2019-11-06
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

Spain - AEMPS

A.2

EudraCT number

2017-002835-40

A.3

Full title of the trial

Topical rVA576 for treatment of atopic keratoconjunctivitis: a randomised placebo double masked parallel trial (TRACKER)

rVA576 tópico para el tratamiento de la queratoconjuntivitis atópica: un ensayo aleatorizado paralelo, doble ciego y controlado con placebo (TRACKER)

A.3.1

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

Topical rVA576 for treatment of atopic keratoconjunctivitis: a randomised placebo double masked parallel trial (TRACKER)

rVA576 tópico para el tratamiento de la queratoconjuntivitis atópica: un ensayo aleatorizado paralelo, doble ciego y controlado con placebo (TRACKER)

A.3.2

Name or abbreviated title of the trial where available

TRACKER

A.4.1

Sponsor's protocol code number

AK701

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	Akari Therapeutics Plc
B.1.3.4	Country	United Kingdom
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	Akari Therapeutics Plc
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Tailored Clinical Research Solutions
B.5.2	Functional name of contact point	Davy Yeung
B.5.3	Address:
B.5.3.1	Street Address	Regal Court Business Centre, 42-44 High St
B.5.3.2	Town/ city	Slough
B.5.3.3	Post code	SL1 1EL
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	07776070005
B.5.6	E-mail	davy.yeung@tcr-solutions.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	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	rVA576
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	Not available
D.3.9.2	Current sponsor code	rVA576
D.3.9.4	EV Substance Code	SUB182098
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	2.5
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	Yes
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Eye drops, solution
D.8.4	Route of administration of the placebo	Ocular use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Moderate to severe atopic keratoconjunctivitis (AKC),
Vernal keratoconjunctivitis (VKC),
Severe allergic conjunctivitis (seasonal (SAC) or perennial (PAC))

Queratoconjuntivitis atópica de moderada a severa (AKC),
Queratoconjuntivitis vernal (VKC),
Conjuntivitis alérgica severa (estacional (SAC) o permanente (PAC))

E.1.1.1

Medical condition in easily understood language

A chronic (long-term) allergic condition of the eyelids and front surface of the eye

Una condición alérgica crónica (a largo plazo) de los párpados y la superficie frontal del ojo.

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	10069664
E.1.2	Term	Atopic keratoconjunctivitis
E.1.2	System Organ Class	10015919 - Eye disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	PT
E.1.2	Classification code	10081000
E.1.2	Term	Vernal keratoconjunctivitis
E.1.2	System Organ Class	10015919 - Eye disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10081002
E.1.2	Term	Vernal keratoconjunctivitis perennial
E.1.2	System Organ Class	10015919 - Eye disorders

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	10001709
E.1.2	Term	Allergic conjunctivitis
E.1.2	System Organ Class	10015919 - Eye disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of the study is to assess safety and tolerability (how well the patient copes with the drug) of topical rVA576 for patients with moderate to severe atopic keratoconjunctivitis (AKC), vernal keratoconjunctivitis (VKC) and severe allergic conjunctivitis (seasonal (SAC) or perennial (PAC))

El objetivo principal del estudio es evaluar la seguridad y la tolerabilidad (cómo de bien el paciente tolera el medicamento) de rVA576 tópico para pacientes con queratoconjuntivitis atópica de moderada a severa (AKC), queratoconjuntivitis vernal (VKC) y conjuntivitis alérgica severa(estacional (SAC) ) o perenne (PAC))

E.2.2

Secondary objectives of the trial

The secondary objective of the study is to assess the efficacy (how well it works) of topical rVA576 in patients with moderate to severe atopic keratoconjunctivitis (AKC), vernal keratoconjunctivitis (VKC) and severe allergic conjunctivitis (seasonal (SAC) or perennial (PAC))

El objetivo secundario del estudio es evaluar la eficacia (cómo de bien funciona) del rVA576 tópico en pacientes con queratoconjuntivitis atópica de moderada a severa (AKC), queratoconjuntivitis vernal (VKC) y conjuntivitis alérgica severa (estacional (SAC) o perenne (PAC))

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients must meet the following criteria in order to be included in the study:
Inclusion Criteria:
1. Aged 18 and above
2. Diagnosis of moderate to severe AKC, VKC, or severe allergic conjunctivitis (seasonal or perennial). Defined as:
• AKC, VKC - a composite symptom/sign score from one eye of ≥ 18 out of 33 (see Clinical Scoring Section 17.1)
• Severe allergic conjunctivitis (SAC or PAC) - a composite symptom/sign score from one eye of ≥ 15 out of 27 (see Clinical Scoring Section 17.2)
3. Will have had received some topical therapy during the last 3 months without improvement but will not currently be receiving systemic immunotherapy. Topical therapy may be topical cyclosporin, antihistamines or corticosteroids alone or in combination. Lubricants or artificial tears will not a count as topical therapy for these purposes.
4. Will have had at least 7 days without topical ocular corticosteroids prior to entry
5. Willing to give informed consent
6. Willing to use highly effective contraceptive precautions for the duration of the study and for 90 days after the last dose of IMP
7. Willing to avoid prohibited medications for duration of study (see list of prohibited medications)

Los pacientes deben cumplir los siguientes criterios para ser incluidos en el estudio:
Criterios de inclusión:
1. Mayores de 18 años
2. Diagnóstico de AKC de moderada a severa, VKC o conjuntivitis alérgica severa (estacional o permanente). Definido como:
• AKC, VKC - puntuación compuesta de síntoma/signo de un ojo de ≥ 18 de 33 (ver Sección de Puntuación Clínica17.1)
• Conjuntivitis alérgica severa (SAC o PAC) - puntuación compuesta de síntoma/signo de un ojo de ≥ 15 de 27 (ver Sección de Puntuación Clínica17.2)
3. Habría recibido alguna terapia tópica durante los últimos 3 meses sin mejoría, pero actualmente no recibe inmunoterapia sistémica. La terapia tópica puede ser ciclosporina tópica, antihistamínicos o corticosteroides solos o en combinación. Los lubricantes o las lágrimas artificiales no contarán como terapia tópica para estos fines.
4. Haber estado al menos 7 días sin corticosteroides oculares tópicos antes de la incorporación al estudio
5. Dispuesto a dar su consentimiento informado
6. Dispuesto a utilizar precauciones anticonceptivas altamente efectivas durante el estudio y durante 90 días después de la última dosis del MEI (medicamento en investigación)
7. Dispuesto a evitar los medicamentos prohibidos durante la duración del estudio (ver lista de medicamentos prohibidos)

E.4

Principal exclusion criteria

A patient will not be eligible for the study if he/she meets one or more of the following criteria:
Exclusion Criteria:
1. Eye surface disease other than AKC, VKC or severe allergic conjunctivitis (SAC or PAC)
2. Contact lens use during the study
3. Complete or partial tarsorrhaphy. If such a procedure becomes necessary during the course of the trial patients may remain in the trial providing that at least 50% of the eye surface remains visible to slit lamp examination
4. Ankyloblepharon of any degree at entry to the trial
5. Known or suspected ocular malignancy
6. Active ocular infection at entry to the trial. Patients with eye surface bacterial, viral, fungal or protozoal infection may enter the trial after elimination of the infection as confirmed by eye swabs
7. Known or suspected uveitis
8. Participation in any other clinical trial within 1 month of enrolment
9. Use of any of the following prohibited medications:
• Eculizumab
• Any other investigational complement inhibitor whether systemic or topical (e.g. RA101495)
• Montelukast
• Zafirlukast
• Pranlukast
• Zileuton
• Hypericum perforatum (St John’s wort)
10. Corneal perforation
11. Uncontrolled glaucoma (increase in dose of glaucoma medication or surgical intervention for glaucoma within 3 months prior to entry)
12. Pregnancy (females)
13. Breast feeding (females)
14. Known allergy to ticks or severe reaction to arthropod venom (e.g. bee or wasp venom)
15. Use of topical ocular steroids within 7 days of the Screening visit
16. Failure to satisfy the PI of suitability to participate for any other reason

Un paciente no será elegido para el estudio si cumple con uno o más de los siguientes criterios:
Criterio de exclusión:
1. Enfermedad de la superficie ocular que no sea AKC, VKC o conjuntivitis alérgica severa (SAC o PAC)
2. Uso de lentillas durante el estudio
3. Tarsorrafia completa o parcial. Si dicho procedimiento se hace necesario durante el transcurso del ensayo, los pacientes pueden mantenerse en el mismo siempre que al menos el 50 % de la superficie ocular sea visible para el examen con lámpara de hendidura.
4. Anquilobléfaron de cualquier grado al incorporarse al ensayo
5. Malignidad ocular conocida o sospechada
6. Infección ocular activa al incorporarse al ensayo. Los pacientes con infección bacteriana, viral, fúngica o protozoaria de la superficie ocular pueden incorporarse al ensayo una vez erradicada la infección, según lo confirmen los hisopos
7. Uveítis conocida o sospechada
8. Participación en cualquier otro ensayo clínico en el periodo de 1 mes de la inscripción
9. Uso de cualquiera de los siguientes medicamentos prohibidos:
• Eculizumab
• Cualquier otro inhibidor del complemento en investigación, ya sea sistémico o tópico (por ej., RA101495)
• Montelukast
• Zafirlukast
• Pranlukast
• Zileutón
• Hypericum perforatum (hierba de San Juan)
10. Perforación corneal
11. Glaucoma no controlado (aumento de la dosis de medicación para el glaucoma o intervención quirúrgica del glaucoma dentro de los 3 meses anteriores a la incorporación)
12. Embarazo (mujeres)
13. Lactancia (mujeres)
14. Alergia conocida a garrapatas o reacción severa al veneno de artrópodos (por ej., veneno de abeja o avispa)
15. Uso de esteroides oculares tópicos dentro de los 7 días de la visita de selección
16. El IP decide la no idoneidad para participar por cualquier otro motivo

E.5 End points

E.5.1

Primary end point(s)

Incidence of ocular treatment emergent adverse events during the treatment period (adverse events which have occurred during the 56 days following randomisation (Part 2 of the study only) will be considered in the analysis of the primary safety outcome).

La incidencia de los eventos adversos emergentes del tratamiento ocular durante el período de tratamiento (los eventos adversos que ocurrieron durante los 56 días posteriores a la aleatorización (solo la Parte 2 del estudio) se considerarán en el análisis del resultado de seguridad primario).

E.5.1.1

Timepoint(s) of evaluation of this end point

Evaluations at Day 1, 14, 28, 42, 56 and 84.

Evaluaciones en los días 1, 14, 28, 42, 56 y 84.

E.5.2

Secondary end point(s)

Secondary Endpoints will include:
• Post-instillation comfort, as graded on patient diary cards at the following intervals Days 1-14, Day 15-28, Day 29-42 and Day 43-56
• Visual acuity by Early Treatment Diabetic Retinopathy Study (ETDRS) charts comparison from Day 1 to Day 56
• Change from Day 1 in composite clinical scores at Day 14, 28, 42 and 56
• Number and percentage of patients with MMP-9 positive levels at Days 1, 28 and 56
• Change from Day 1 in Tear film break up time (TBUT) at Day 14, 28, 42 and 56

Los criterios secundarios de valoración incluirán:
• Confort posterior a la instilación, tal como se califica en las tarjetas del diario del paciente, en los siguientes intervalos: días 1-14, día 15-28, día 29-42 y día 43-56
• Comparación de gráficos de agudeza visual según el Estudio del Tratamiento Temprano de la Retinopatía Diabética (ETDRS) del día 1 al día 56
• Cambio desde el día 1 en puntuaciones clínicas compuestas en los días 14, 28, 42 y 56
• Número y porcentaje de pacientes con niveles positivos de MMP-9 en los días 1, 28 y 56
• Cambio desde el día 1 en el tiempo de ruptura de la película lagrimal (TBUT) en los días 14, 28, 42 y 56

E.5.2.1

Timepoint(s) of evaluation of this end point

Evaluations at Day 1, 14, 28, 42 and 56

Evaluaciones en los días 1, 14, 28, 42 y 56

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

Yes

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

Tolerabilidad

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

A phase I/II study looking at the safety and tolerability of topical rVA576

Un estudio de fase I/II que analiza la seguridad y la tolerabilidad de rVA576 tópico

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

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

Yes

E.8.1.7.1

Other trial design description

un ensayo aleatorizado paralelo, doble ciego y controlado con placebo

a randomised placebo controlled double masked parallel trial

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

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

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

Última visita del último paciente

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)

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

F.3.3.1

Women of childbearing potential not using contraception