Clinical Trials Register

Summary
EudraCT Number:	2016-004119-11
Sponsor's Protocol Code Number:	SPECT
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2016-11-09
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

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A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2016-004119-11

A.3

Full title of the trial

Study on half-dose Photodynamic therapy versus Eplerenone in chronic CenTRAl serous chorioretinopathy (SPECTRA trial)

Studie naar halve dosis fotodynamische therapie versus eplerenon bij chronische centrale sereuze chorioretinopathie (SPECTRA studie)

A.3.1

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

Photodynamic therapy versus eplerenone in chronic central serous chorioretinopathy

Fotodynamische therapie versus eplerenon bij chronische centrale sereuze chorioretinopathie

A.3.2

Name or abbreviated title of the trial where available

SPECTRA

A.4.1

Sponsor's protocol code number

SPECT

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	Leiden University Medical Center
B.1.3.4	Country	Netherlands
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	Leiden University Medical Center
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Leiden University Medical Center
B.5.2	Functional name of contact point	Clinical Trial Information
B.5.3	Address:
B.5.3.1	Street Address	Albinusdreef 2
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	2333ZA
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	31715299431

D. IMP Identification
D.IMP: 1
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	eplerenone
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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	eplerenone
D.3.2	Product code	SPECT
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	eplerenone
D.3.9.1	CAS number	107724-20-9
D.3.9.2	Current sponsor code	SPECT
D.3.9.3	Other descriptive name	EPLERENONE
D.3.9.4	EV Substance Code	SUB06574MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	25 to 50
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

Chronic central serous chorioretinopathy

Chronische centrale sereuze chorioretinopathie

E.1.1.1

Medical condition in easily understood language

Chronic CSC

Chronische serosa

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	19.0
E.1.2	Level	PT
E.1.2	Classification code	10063118
E.1.2	Term	Chorioretinopathy
E.1.2	System Organ Class	10015919 - Eye disorders

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 investigate whether half-dose PDT treatment leads to a higher percentage of cCSC patients with SRF on OCT at baseline, achieving an absence of this SRF on OCT as compared to eplerenone treatment.

Onderzoeken of halve dosis fotodynamische therapie in cCSC patiënten met subretinaal vocht op OCT tijdens het Baseline bezoek leidt tot een hoger percentage patiënten met een afwezigheid van dit vocht, in vergelijking met eplerenon behandeling.

E.2.2

Secondary objectives of the trial

To investigate the clinical outcome comparing half-dose PDT treatment with eplerenone treatment in patients with SRF due to active leakage in cCSC, based on evaluation of best-corrected visual acuity (BCVA), retinal sensitivity on microperimetry, and subjective scores on the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25).

Onderzoeken van de klinische uitkomst van behandeling van cCSC patiënten met subretinaal vocht op OCT door actieve lekkage, middels halve dosis fotodynamische therapie versus middels eplerenon: evaluatie op basis van best-gecorrigeerde visus, retinale sensitiviteit bij onderzoek middels microperimetrie, en subjectieve scores bij beantwoorden van de National Eye Institute Visual Function Questionnaire (NEI-VFQ-25).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

This study will enroll subjects with cCSC with active leakage of fluid to under the retina as evidenced on OCT scanning and further supported by findings on FA and ICGA, in at least 1 eye, who visit the outpatient clinic of the Department of Ophthalmology of the Radboud University Medical Center, the Academic Medical Center Amsterdam, or the Leiden University Medical Center. If both eyes are eligible, then the eye with the longer duration of disease will be used as the study eye, except in cases where the disease is present > 18 months. In the latter case, which is an exclusion criterion, the other eye will be eligible for inclusion if the disease is active for < 18 months in that eye. If the non-study eye also has active disease, the choice to treat and the type of treatment in this eye may be chosen freely at the discretion of the responsible ophthalmologist.
Before enrolment, each subject must meet all of the following inclusion criteria and none of the exclusion criteria, and agree to comply with the study requirements including completion of all of the study visits.

In order to be eligible to participate in this study, a subject must meet all of the following criteria:
- Age of ≥ 18 years of age and able to give written IC;
- Active cCSC;
- Subjective visual loss > 6 weeks, interpreted as onset of active disease;
- Foveal SRF on OCT, at Baseline Examination;
- ≥1 ill-defined hyperfluorescent leakage areas on FA with RPE window defect(s) that are compatible with cCSC;
- Hyperfluorescent areas on ICGA.

CCSC patiënten met actieve lekkage van vocht naar onder het netvlies, in minimaal één oog en bewezen op OCT en verder ondersteund door bevindingen op FA en ICGA, kunnen worden geïncludeerd in één van de drie deelnemende studiecentra. Wanneer beide ogen van een patiënt zouden kunnen worden geïncludeerd, wordt het oog gekozen waarin de ziekteduur het langst is (tenzij die duur >18 maanden is). Het oog dat in dat geval niet in de studie wordt geïncludeerd, kan worden behandeld op basis van de expertise van de behandelend oogarts.

Inclusiecriteria voor de studie zijn:
- Leeftijd van boven de 18 jaar en in staat tot geven van geschreven informed consent;
- Actieve cCSC;
- Subjectieve visusklachten gedurende >6 weken, welke geïnterpreteerd zijn als start van actieve ziekte;
- Foveaal subretinaal vocht op OCT, tijdens Baseline Evaluatie;
- Eén of meer ziektespecifieke hyperfluorescente lekkage gebieden op FA, met RPE window defecten die compatibel zijn met cCSC;
- Hyperfluorescente gebieden op ICGA.

E.4

Principal exclusion criteria

A potential subject who meets any of the following criteria for the study eye will be excluded from participation in this study:
- Any previous treatments for active CSC;
- Previous prescription of mineralocorticoid receptor antagonists, for cCSC or for other diseases;
- Current treatment with corticosteroids (topical or systemic), corticosteroid use within 3 months before possible start of trial treatment, or anticipated start of corticosteroid treatment within the first 2 years from the start of the trial period;
- Evidence of another diagnosis that can explain serous SRF or visual loss;
- BCVA < 20/200 (Snellen equivalent);
- Profound chorioretinal atrophy in central macular area on ophthalmoscopy and OCT;
- Myopia > 6D;
- Visual loss and/or serous detachment on OCT < 6 weeks;
- Continuous and/or progressive visual loss > 18 months or serous detachment on OCT > 18 months;
- No hyperfluorescence on ICGA;
- Intraretinal edema on OCT;
- (relative) Contraindications for FA or ICGA;
- (relative) Contraindications for PDT treatment (pregnancy, porphyria, severely disturbed liver function). Pregnancy will not be routinely tested in female patients, but the possibility of pregnancy will be discussed during screening;
- (relative) Known contraindications for initiation of eplerenone treatment (hyperkalemia, abnormal renal clearance, severe hepatic insufficiency (Child-Pugh C), type 2 diabetes mellitus with microalbuminuria, concomitant use of potassium supplements, potassium-sparing diuretics, strong CYP3A4 inhibitors, or the combination of an ACE-inhibitor and an angiotensin receptor blocking agent). Pregnancy will not be routinely tested in female patients, but the possibility of pregnancy will be discussed during screening;
- Soft drusen in treated eye or fellow eye, signs of choroidal neovascularization on ophthalmoscopy and/or FA/ICGA of the study eye.

The previous prescription of oral medication (for example, acetazolamide) for cCSC, except the prescription of previous mineralocorticoid receptor antagonists, is not an exclusion criterion for this study.

Exclusiecriteria voor deze studie:
- Elke eerdere behandeling voor actieve cCSC;
- Eerdere voorschrijving van mineralocorticoïd receptor antagonisten, zowel voor de behandeling van cCSC als voor de behandeling van eerdere ziekte(n);
- Huidige behandeling met corticosteroïden (topicaal of systemisch), corticosteroïdgebruik binnen drie maanden voor de mogelijke start van trialbehandeling, of voorgenomen start van corticosteroïdbehandeling binnen de eerste twee jaar na start van trialbehandeling;
- Bewijs van een andere diagnose die het bestaan van sereus subretinaal vocht en/of visusklachten zou kunnen verklaren;
- Best-gecorrigeerde visus <20/200 (Snellen);
- Duidelijke chorioretinale atrofie in het centrale maculaire gebied, bij oftalmoscopie en OCT;
- Myopie >6D;
- Visusklachten en/of sereuze loslating op OCT van <6 weken;
- Continue en/of progressieve visusklachten van >18 maanden of een sereuze loslating op OCT van >18 maanden;
- Geen hyperfluorescente gebieden op ICGA;
- Intraretinaal oedeem op OCT;
- (relatieve) contraindicaties voor FA of ICGA;
- (relatieve) contraindicaties voor PDT behandeling;
- (relatieve) contraindicatie voor eplerenon behandeling;
- Zachte drusen in één van beide ogen, tekenen van een choroïdale neovascularisatie, bij oftalmoscopie en/of FA/ICGA van het studieoog.

Eerdere voorschrijving van orale medicijnen (bijvoorbeeld: acetazolamide) voor cCSC, behalve de voorschrijving van eerdere mineralocorticoïd receptor antagonisten, is geen exclusiecriterium voor inclusie in de studie.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint of this study is to assess if there is a difference between half-dose PDT and eplerenone treatment in patients with cCSC, in terms of complete resolution of SRF on OCT. The assessment of this efficacy will be based on the anatomical effect on OCT: absence of SRF versus persistence of SRF, at 3 months after the initiation of treatment.

Verschil in complete resolutie van subretinaal vocht op OCT (complete resolutie versus persisterend subretinaal vocht) in de patiënten die met fotodynamische therapie behandeld zijn, versus de patiënten die met eplerenon behandeld zijn.

E.5.1.1

Timepoint(s) of evaluation of this end point

At 3 months after the initiation of treatment

Drie maanden na start van behandeling.

E.5.2

Secondary end point(s)

As secondary endpoints, we will mainly look at 3 parameters that reflect the patient’s vision-related functioning. These 3 parameters are: a standardized measurement of ETDRS BCVA, a standardized measurement of sensitivity of the macula with microperimetry, and a standardized assessment of the patient’s vision-related quality of life using a validated questionnaire, the NEI-VFQ-25.

The secondary endpoints that will be assessed as a reflection of functional improvement after treatment include:
- Number of cross-over treatments (eplerenone after half-dose PDT, and half-dose PDT after eplerenone) needed in each treatment arm;
- Mean change in ETDRS BCVA in the study eye at Evaluation Visit 1, at – if applicable – Evaluation Visit 2, at Evaluation Visit 3, and at the Final Evaluation Visit, compared to Baseline Evaluation;
- Mean change in ETDRS BCVA in the study eye at Evaluation Visit 3 and at Final Evaluation Visit among those with subsequent (cross-over) and those without subsequent treatment;
- Mean change in retinal sensitivity in the study eye at Evaluation Visit 1, at – if applicable – Evaluation Visit 2, at Evaluation Visit 3, and at Final Evaluation Visit, compared to Baseline Evaluation;
- Mean change in the NEI-VFQ-25 questionnaire at Evaluation Visit 1, at – if applicable – Evaluation Visit 2, at Evaluation Visit 3, and at Final Evaluation Visit, compared to Baseline Evaluation;
- The long-term outcome both after successful treatment and after non-successful treatment (‘success’ is defined as the absence of SRF on OCT at Evaluation Visit 1 (at 3 months after the initiation of treatment));
- Differences between starting with treatment A with the possibility to switch to treatment B compared to starting with treatment B with the possibility to switch to treatment A;
- The number of (S)AEs in the 2 different treatment groups.

Secundaire eindpunten van deze studie zijn drie parameters die het visueel functioneren van patiënten weergeven: gestandaardiseerde meting van best-gecorrigeerde visus in ETDRS letters, gestandaardiseerde meting van maculaire sensitiviteit bij onderzoek middels microperimetrie, en een gestandaardiseerd onderzoek van de kwaliteit van visueel functioneren van patiënten, waarbij gebruikt wordt gemaakt van de NEI-VFQ-25 vragenlijst.

Secundaire eindpunten van deze studie zijn:
- Aantal cross-over behandelingen in de twee behandelarmen van de studie;
- Gemiddelde verandering in best-gecorrigeerde visus in ETDRS letters in het studieoog tijdens Evaluatiebezoek 1 (drie maanden na start van de trialbehandeling), tijdens - indien van toepassing - Evaluatiebezoek 2 (drie maanden na mogelijke cross-over over behandeling binnen de trial), tijdens Evaluatiebezoek 3 (één jaar na start van trial behandeling), en tijdens Evaluatiebezoek 4 (twee jaar na start van trial behandeling) - alle ten opzichte van Baseline Evaluatie;
- Gemiddelde verandering in best-gecorrigeerde visus in ETDRS letters in het studieoog tijdens Evaluatiebezoek 3 en tijdens het Laatste Evaluatiebezoek, waarbij patiënten met een cross-over behandeling worden vergeleken met patiënten die geen cross-over behandeling binnen de trial ontvingen;
- Gemiddelde verandering in retinale sensitiviteit bij microperimetrie in het studieoog tijdens Evaluatiebezoek 1 (drie maanden na start van de trialbehandeling), tijdens - indien van toepassing - Evaluatiebezoek 2 (drie maanden na mogelijke cross-over over behandeling binnen de trial), tijdens Evaluatiebezoek 3 (één jaar na start van trial behandeling), en tijdens Evaluatiebezoek 4 (twee jaar na start van trial behandeling) - alle ten opzichte van Baseline Evaluatie;
- Gemiddelde verandering in de uitkomst van beantwoording van vragen van NEI-VFQ-25, tijdens Evaluatiebezoek 1 (drie maanden na start van de trialbehandeling), tijdens - indien van toepassing - Evaluatiebezoek 2 (drie maanden na mogelijke cross-over over behandeling binnen de trial), tijdens Evaluatiebezoek 3 (één jaar na start van trial behandeling), en tijdens Evaluatiebezoek 4 (twee jaar na start van trial behandeling) - alle ten opzichte van Baseline Evaluatie;
- Lange termijn uitkomst na succesvolle behandeling en niet-succesvolle behandeling binnen de trial ('succes' is hierbij gedefinieerd als de afwezigheid van subretinaal vocht op OCT tijdens het Eerste Evaluatiebezoek (na 3 maanden na start van behandeling);
- Verschillen tussen starten met behandeling A en de mogelijkheid is te switchen naar behandeling B, en starten met behandeling B en de mogelijkheid te switchen naar behandeling A;
- Aantal (S)AEs in de twee verschillende behandelarmen.

E.5.2.1

Timepoint(s) of evaluation of this end point

At Evaluation Visit 1 (at 3 months after the start of trial treatment), at – if applicable – Evaluation Visit 2 (at 3 months after possible cross-over trial treatment), at Evaluation Visit 3 (one year after the start of trial treatment), and at the Final Evaluation Visit (two years after the start of trial treatment), compared to Baseline Evaluation;

Tijdens Evaluatiebezoek 1 (drie maanden na start van de trialbehandeling), tijdens - indien van toepassing - Evaluatiebezoek 2 (drie maanden na mogelijke cross-over over behandeling binnen de trial), tijdens Evaluatiebezoek 3 (één jaar na start van trial behandeling), en tijdens Evaluatiebezoek 4 (twee jaar na start van trial behandeling) - alle ten opzichte van Baseline Evaluatie.

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)

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

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

E.8.1.6

Cross over

Yes

E.8.1.7

Other

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

half-dose verteporfin photodynamic therapy

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

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

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

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

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:

100

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

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

107

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)

At the discretion of the treating ophthalmologist.

Op basis van de expertise van de behandelend oogarts.

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

2016-11-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-12-19

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

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