Clinical Trials Register

Summary
EudraCT Number:	2019-003514-14
Sponsor's Protocol Code Number:	CL2-62798-010
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:	2020-05-06
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

2019-003514-14

A.3

Full title of the trial

A Multicentre, Randomized, Double-blind, Placebo-controlled Dose-finding Study of S62798 in Patients with Intermediate-High Risk Acute Pulmonary Embolism on heparin

Estudio multicéntrico, aleatorizado, doble ciego, controlado con placebo de búsqueda de dosis de S62798 en pacientes con tromboembolia pulmonar aguda de riesgo intermedio-alto en tratamiento con heparina

A.3.1

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

A study to find the appropriate dose of S62798 to treat patients with pulmonary circulation blocked by a clot

Un estudio para encontrar la dosis adecuada de S62798 para tratar pacientes con circulación pulmonar bloqueada por un coagulo

A.4.1

Sponsor's protocol code number

CL2-62798-010

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	Institut de Recherches Internationales Servier
B.1.3.4	Country	France
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	ADIR
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Institut de Recherches Internationales Servier (I.R.I.S)
B.5.2	Functional name of contact point	Clinical Studies Department
B.5.3	Address:
B.5.3.1	Street Address	50 rue Carnot
B.5.3.2	Town/ city	SURESNES CEDEX
B.5.3.3	Post code	92284
B.5.3.4	Country	France
B.5.4	Telephone number	+331 55724366
B.5.5	Fax number	+331 55725412
B.5.6	E-mail	clinicaltrials@servier.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	S62798
D.3.2	Product code	S62798
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	S62798
D.3.9.2	Current sponsor code	S62798
D.3.9.3	Other descriptive name	S62798
D.3.9.4	EV Substance Code	SUB184588
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	0.2
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	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	S62798
D.3.2	Product code	S62798
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	S62798
D.3.9.2	Current sponsor code	S62798
D.3.9.3	Other descriptive name	S62798
D.3.9.4	EV Substance Code	SUB184588
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	0.6
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: 3
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	S62798
D.3.2	Product code	S62798
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	S62798
D.3.9.2	Current sponsor code	S62798
D.3.9.3	Other descriptive name	S62798
D.3.9.4	EV Substance Code	SUB184588
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	1.3
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: 4
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	S62798
D.3.2	Product code	S62798
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	S62798
D.3.9.2	Current sponsor code	S62798
D.3.9.3	Other descriptive name	S62798
D.3.9.4	EV Substance Code	SUB184588
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	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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Concentrate for solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Acute intermediate high risk pulmonary embolism (PE)

Tromboembolia pulmonar (TEP) aguda de riesgo intermedio-alto

E.1.1.1

Medical condition in easily understood language

Pulmonary circulation blocked by a clot

Circulación pulmonar bloqueada por un coagulo

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

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	10037377
E.1.2	Term	Pulmonary embolism
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal 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

To determine the dose-response relationship of S62798 on the RV/LV end-diastolic diameter (EDD) 24h after treatment initiation, in patients with intermediate-high risk pulmonary embolism (PE) on heparin.

El objetivo principal del estudio es determinar la relación dosis-respuesta de S62798 sobre la relación VD/VI de los diámetros diastólicos finales (DDF) 24 h después del inicio del tratamiento, en pacientes con riesgo intermedio-alto de tromboembolia pulmonar (TEP) tratados con heparina.

E.2.2

Secondary objectives of the trial

To assess the effect of S62798 on secondary efficacy endpoints such as TAPSE, and PE-related clinical events.
To assess the safety profile of S62798 in the study population.
To assess the pharmacokinetics of S62798 (and metabolites if applicable).

Valorar el efecto de S62798 sobre las variables exploratorias de eficacia como TAPSE y eventos clínicos relacionados con TEP.
Valorar el perfil de seguridad de S62798 en la población del estudio.
Valorar las farmacocinéticas de S62798 en la población del estudio (y metabolitos si aplica).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Acute pulmonary embolism and categorized as intermediate-high risk and documented by CT pulmonary angiography (CTPA), V/Q scan, V/Q SPECT or pulmonary angiography with emboli in at least one segmental or more proximal artery
2. Troponin I or high sensitivity Troponin T elevated as per local lab
3. Evidence of right ventricular dysfunction (RVD) on echocardiography or CTPA
4. With at least one of the following clinical criteria:
o SBP lower than 110 mmHg for > 15 min or,
o Respiratory rate > 20 per min or SaO2 < 90% on room air or,
o Sinus tachycardia ≥ 110 bpm sustained over 30 seconds.

1. Tromboembolia pulmonar categorizada como riesgo intermedio-alto y documentada mediante una angiografía pulmonar por TC (APTC), gammagrafía V/Q, V/Q SPECT o angiografía pulmonar con un émbolo en al menos una arteria segmentaria o más proximal.
2. Troponina I o Troponina T de alta sensibilidad elevadas según valores del laboratorio local.
3. Evidencia de disfunción del VD valorada mediante ecocardiografía o APTC.
4. Con al menos uno de los siguientes criterios;
o TA sistólica menor de 110 mmHg durante > 15 min o,
o Frecuencia respiratoria > 20 por min o SaO2 < 90% en aire ambiente o,
o Taquicardia sinusal ≥ 110 lpm sostenida durante más de 30 segundos

E.4

Principal exclusion criteria

1. Presence of right heart thrombus
2. Reperfusion therapy planned.
3. Patients with forbidden previous or concomitant treatment
4. Known or pre-existing chronic pulmonary hypertension
5. Uncontrolled hypertension defined as SBP>180 mm Hg and/or DBP >110 mm Hg
6. Patients with a high risk of haemorrhage
7. Patients with less than 3 months of life expectancy
8. Platelet count lower than 100 G/L (100 000 platelets/µL), INR above 1.5 or abnormal aPTT not explained by concomitant anticoagulation therapy
9. Positive results of pregnancy test or lacting women

1. Presencia de trombo cardíaco derecho
2. Terapia de reperfusion planeada
3. Pacientes con tratamiento previo o concomitante prohibido
4. Hipertensión pulmonar crónica conocida o preexistente
5. Hipertensión no controlada definida como TA sistólica > 180 mm Hg y/o TA diastólica > 110 mm Hg
6. Pacientes con alto riesgo de hemorragia
7. Pacientes con menos de 3 meses de esperanza de vida
8. Recuento de plaquetas inferior a 100 G/L (100 000 plaquetas/µL), INR superior a 1,5 o aPTT anormal no explicado por el tratamiento anticoagulante concomitante
9. Resultados positivos de la prueba de embarazo o mujeres lactantes

E.5 End points

E.5.1

Primary end point(s)

Right /left ventricular end-diastolic diameter (RV/LV EDD)

relación VD/VI de los diámetros diastólicos finales (VD/VI DDF)

E.5.1.1

Timepoint(s) of evaluation of this end point

24h (±2h) after treatment initiation

24 h (±2h) después del inicio del tratamiento

E.5.2

Secondary end point(s)

1. RV/LV EDD
2. Tricuspid annular plane systolic excursion (TAPSE) estimated by echocardiography
3. Adjudicated PE-related clinical events
4. Pharmacokinetic measurements

1. VD/VI DDF
2. Desplazamiento sistólico del plano del anillo tricuspideo (TAPSE) estimado mediante ecografía
3. Acontecimientos clínicos considerados relacionados con la TEP
4. Medidas farmacocinéticas

E.5.2.1

Timepoint(s) of evaluation of this end point

1. For RV/LV EDD: 48h (±4h) and 30d (±2d)
2. For tricuspid annular plane systolic excursion (TAPSE) estimated by echocardiography: 24h (±2h), 48h (±4h) and 30d (±2d)
3. For adjudicated PE-related clinical events: Between baseline and day 30
4. For pharmacokinetic measurements: Between baseline and day 6

1. VD/VI DDF a las 48h (±4 h) y 30d (± 2 d)
2. Desplazamiento sistólico del plano del anillo tricuspideo (TAPSE) estimado mediante ecografía a las 24 h (+/-2h), 48 h (+/- 4 h) y 30 d (+/-2d)
3. Acontecimientos clínicos considerados relacionados con la TEP: Entre basal y día 30
4. Medidas farmacocinéticas: Entre basal y día 6

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

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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

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)

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

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

Argentina

Austria

Belgium

Brazil

Czech Republic

Estonia

Finland

Germany

Greece

Hungary

Israel

Italy

Japan

Korea, Republic of

Latvia

Lithuania

Poland

Portugal

Romania

Russian Federation

Slovakia

South Africa

Spain

Taiwan

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

End of Trial is defined as the date of the last follow-up of the last participant, or the date of the last contact attempt if the last participant is declared lost to follow-up.

El final del ensayo se define como la fecha de la última visita de seguimiento del último paciente participante, o la fecha del último intento de contacto si el último paciente participante es declarado perdida de seguimiento.

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

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:

185

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

185

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

Yes

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

258

F.4.2.2

In the whole clinical trial

370

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)

The participants' treatment is left to the physician's discretion. As the study drug is not licensed yet at this time, it will not be available on the market.

El tratamiento de los participantes se deja a elección del médico. Como el medicamento del estudio aún no está aprobado, no estará disponible en el mercado.

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

2020-04-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-01-10

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2020-07-15

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