Clinical Trials Register

Summary
EudraCT Number:	2017-002454-36
Sponsor's Protocol Code Number:	2125-MEL-301
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:	2018-11-05
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

2017-002454-36

A.3

Full title of the trial

A Randomized Phase 3 Comparison of IMO-2125 with Ipilimumab versus Ipilimumab Alone in Subjects with Anti-PD-1 Refractory Melanoma

Comparación randomizada de fase III de IMO-2125 con ipilimumab frente a ipilimumab en monoterapia en sujetos con melanoma resistente al tratamiento con anti-PD-1

A.3.1

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

A Clinical Trial to compare the effectiveness of the study drug IMO-2125 given in combination with Ipilimumab (a drug indicated for the treatment of advanced melanoma) compared to Ipilimumab given alone in subjects with Refractory Melanoma

Ensayo Clínico para comparer la eficacia del medicamento IMO-2125 suministrado en combinación con Ipilimumab (medicamento indicado para el tratamiento de melanoma avanzado) comparado con Ipilimumab suministrado solo, en pacientes con Melanoma Resistente.

A.4.1

Sponsor's protocol code number

2125-MEL-301

A.5.4

Other Identifiers

Name:

IND number

Number:

125515

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	Idera Pharmaceuticals, Inc.
B.1.3.4	Country	United States
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	Idera Pharmaceuticals, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Idera Pharmaceuticals, Inc.
B.5.2	Functional name of contact point	Michael Bui
B.5.3	Address:
B.5.3.1	Street Address	505 Eagleview Boulevard, Suite 212
B.5.3.2	Town/ city	Exton
B.5.3.3	Post code	PA 19341
B.5.3.4	Country	United States
B.5.4	Telephone number	+16177084286
B.5.6	E-mail	mbui@iderapharma.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	IMO-2125
D.3.2	Product code	IMO-2125
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intratumoral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	tilsotolimod
D.3.9.2	Current sponsor code	tilsotolimod
D.3.9.3	Other descriptive name	IMO-2125
D.3.9.4	EV Substance Code	SUB31305
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	8
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	YERVOY®
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol-Myers Squibb Pharma EEIG
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Ipilimumab
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	IPILIMUMAB
D.3.9.3	Other descriptive name	IPILIMUMAB
D.3.9.4	EV Substance Code	SUB29397
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	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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Refractory melanoma is a malignant tumor of melanocytes which originates predominantly from skin.

El melanoma resistente es un tumor maligno de los melanocitos que se origina principalmente en la piel

E.1.1.1

Medical condition in easily understood language

Refractory melanoma is a type of cancer mainly found on the skin, which may not respond to available treatments.

El melanoma resistente es in tipo de cancer que se encuentra principalmente en la piel, el cual no responde a los tratamientos disponibles

E.1.1.2

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

MedDRA Classification

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	10027481
E.1.2	Term	Metastatic melanoma
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Compare the efficacy measured by overall survival [OS] and overall response rate [ORR] of intratumoral IMO-2125 in combination with ipilimumab versus ipilimumab alone.

Comparar la eficacia (medida mediante la supervivencia global [SG] y la tasa de respuesta global [TRG]) de IMO 2125 intratumoral en combinación con ipilimumab frente a ipilimumab en monoterapia.

E.2.2

Secondary objectives of the trial

Assess other measures of clinical benefit, safety, pharmacokinetics (PK), and patient-reported outcomes (PROs).
Investigate potential biomarkers and the incidence of anti-IMO-2125 antibodies.

Evaluar otras medidas de beneficio clínico, seguridad, farmacocinética (FC) y resultados comunicados por el propio paciente (RCPs).
Investigar los posibles biomarcadores y la incidencia de anticuerpos anti IMO-2125.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subjects must be willing and able to sign the informed consent and comply with the study protocol.
2. Must be ≥18 years of age.
3. Histologically confirmed metastatic melanoma with measurable (by RECIST v1.1), stage III (lymph node or in transit lesions) or stage IVA, IVB, or IVC disease that is accessible for injection.
4. Confirmed progression during or after treatment with either nivolumab or pembrolizumab. Confirmed progression is defined as:
• Radiological progression (confirmed at least 4 weeks after the initial scan showing PD); or
• For progression based solely on worsening of non-target or new, non-measurable disease, confirmation by an additional scan at least 4 weeks after the initial scan unless progression is accompanied by correlative symptoms.
In addition, all the following must hold:
a) No intervening anti-cancer therapy between the last course of nivolumab or pembrolizumab and the first dose of study treatment is allowed except for local measures (e.g., surgical excision or biopsy, focal radiation therapy).
b) The interval between last nivolumab or pembrolizumab and start of study treatment should be at least 21 days with no residual anti-PD-1-related immune toxicities in excess of Grade 1 severity.
c) Subjects who had adjuvant anti-PD-1 treatment are eligible if they have either disease recurrence after the end of adjuvant treatment or on-treatment disease recurrence after ≥12 weeks of adjuvant treatment.
d) If subject BRAF mutation status is unknown, before randomization the subject must have BRAF testing performed using an approved assay method.
e) Patients with BRAF-positive tumor(s) are eligible for the study if they received prior treatment with a BRAF inhibitor (alone or in combination with a MEK inhibitor) or declined targeted therapy.
5. ECOG Performance Status ≤1.
6. Adequate baseline organ function as defined by:
a) Absolute neutrophil count (ANC) ≥1.5 x 109/L (1500/mm3)
b) Platelet count ≥75 x 109/L (75,000/mm3)
c) Hemoglobin ≥8.0 g/dL (4.96 mmol/L)
d) Serum creatinine ≤1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥60 mL/minute (≤Grade 1)
e) Aspartate aminotransferase (AST) ≤2.5 x ULN; alanine aminotransferase (ALT) ≤2.5 x ULN; AST/ALT <5 x ULN if liver involvement (≤Grade 1)
f) Serum bilirubin ≤1.5 x ULN, except in subjects with Gilbert’s Syndrome who must have a total bilirubin <3 mg/dL (≤Grade 1)
7. Women of childbearing potential (WOCBP) and men must agree to use effective contraceptive methods from screening until at least 90 days after the last dose of either ipilimumab or IMO-2125, whichever is later.
8. WOCBP must have a negative pregnancy test (serum or urine) according to the Schedule of Evaluations described in the study Protocol.

1.El paciente debe estar dispuesto y ser capaz de firmar un consentimiento informado y de cumplir el protocolo del estudio.
2.Ser mayor de edad.
3.Presentar melanoma metastásico confirmado histológicamente con enfermedad medible (mediante los criterios de evaluación de la respuesta en tumores sólidos [RECIST] v1.1), en estadio III (ganglio linfático o en lesiones en tránsito) o estadio IVA, IVB o IVC que es accesible para inyección.
4.Progresión confirmada durante o después del tratamiento con nivolumab o pembrolizumab. La progresión confirmada se define como:
•Progresión radiológica (confirmada, como mínimo, cuatro semanas después de la prueba de imagen inicial en la que se observó progresión de la enfermedad) o
•Para progresión basada exclusivamente en el empeoramiento de una enfermedad no medible, nueva o no considerada diana, confirmación mediante una prueba de imagen adicional como mínimo cuatro semanas después de la inicial a menos que la progresión vaya acompañada de síntomas correlativos.
Además, debe cumplirse todo lo que se expone a continuación:
a)No se permite ningún tratamiento antineoplásico intervencionista entre la última pauta de nivolumab o pembrolizumab y la primera dosis del tratamiento del estudio excepto para medidas locales (por ej., extirpación quirúrgica o biopsia, radioterapia focal).
b)El intervalo entre la última dosis de nivolumab o pembrolizumab y el inicio del tratamiento del estudio debería ser de, como mínimo, 21 días sin que haya reacciones adversas inmunitarias residuales relacionadas con anti-PD-1 superiores a grado 1 en gravedad, seriedad.
c)Los pacientes que hayan recibido tratamiento adyuvante anti-PD-1 son aptos si presentan recidiva de la enfermedad después del tratamiento adyuvante o recidiva de la enfermedad durante el tratamiento después de ≥ 12 semanas del tratamiento adyuvante.
d)Si se desconoce el estado de la mutación del gen BRAF, el paciente se someterá al análisis del gen BRAF mediante un método de ensayo aprobado antes de la randomización.
e)Los pacientes con tumores con positividad para la mutación del gen BRAF son aptos para el estudio si han recibido tratamiento previo con un inhibidor del gen BRAF (en monoterapia o en combinación con un inhibidor de MEK) o rechazaron la terapia dirigida.
5.Estado funcional ≤ 1 en la escala funcional del Eastern Cooperative Oncology Group (ECOG).
6.Función orgánica adecuada en el periodo basal, definida mediante:
a)Cifra absoluta de neutrófilos (CAN) ≥ 1,5 x 109/L (1500/mm3)
b) Recuento de plaquetas ≥75 x 109/L (75.000/mm3)
c)Hemoglobina ≥8,0 g/dl (4,96 mmol/l)
d)Creatinina sérica ≤ 1,5 × límite superior de la normalidad (LSN) o aclaramiento de creatinina calculado ≥60 ml/minuto (≤Grado 1)
e)Aspartato-aminotransferasa (ASAT) ≤ 2,5 × LSN; alanina-aminotransferasa (ALAT) ≤ 2,5 × LSN; ASAT/ ALAT <5 × LSN si presentan afectación hepática (≤Grado 1)
f)Bilirrubina sérica ≤1,5 x LSN, excepto en pacientes con Síndrome de Gilbert que deberán tener una bilirrubina total <3 mg/dl (≤Grado 1)
7.Las mujeres en edad potencialmente fértil (MPF) y los varones deben comprometerse a utilizar métodos anticonceptivos eficaces a partir del screening y, como mínimo, hasta 90 días tras la última dosis de ipilimumab o IMO-2125, lo que sea posterior.
8.Las MPF deben tener una prueba de embarazo negativa (suero u orina) conforme al calendario de evaluaciones

E.4

Principal exclusion criteria

1. Ocular melanoma.
2. Prior therapy with a TLR agonist, excluding topical agents.
3. Prior ipilimumab with the exception of adjuvant treatment completed ≥6 months prior to enrollment.
4. Systemic treatment with IFN-α within the previous 6 months.
5. Known hypersensitivity to any oligodeoxynucleotide.
6. Active autoimmune disease requiring disease modifying therapy at the time of screening.
7. Subjects with a requirement for systemic steroids should be receiving ≤10 mg/day of prednisone (or equivalent) for the 2 weeks preceding start of study treatment.
8. Subjects with another primary malignancy that has not been in remission for at least 3 years with the exception of non-melanoma skin cancer, curatively treated localized prostate cancer with non-detectable prostate-specific antigen, cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Papanicolaou (Pap) smear, and thyroid cancer (except anaplastic).
9. Active systemic infections requiring antibiotics.
10. Known active, hepatitis A, B, or C infection.
11. Known diagnosis of human immunodeficiency virus (HIV) infection.
12. Women who are pregnant or breast-feeding.
13. Prior anaphylactic or other severe infusion reaction associated with human antibody administration that cannot be managed with standard supportive measures.
14. Presence of known central nervous system, meningeal, or epidural metastatic disease. However, subjects with known brain metastases are allowed if the brain metastases are stable for ≥4 weeks before the first dose of study treatment. Stable is defined as neurological symptoms not present or resolved to baseline, no radiologic evidence of progression, and steroid requirement of prednisone ≤10 mg/day or equivalent.
15. Impaired cardiac function or clinically significant cardiac disease.

1.Melanoma ocular.
2.Tratamiento previo con un agonista de TLR, excluidos los fármacos tópicos.
3.Tratamiento previo con ipilimumab a excepción del tratamiento adyuvante finalizado ≥ 6 meses antes de la inclusión.
4.Tratamiento sistémico con IFN-α en el plazo de los seis meses anteriores.
5.Hipersensibilidad conocida a cualquier oligodesoxinucleótido.
6.Enfermedad autoinmunitaria activa que precise tratamiento modificador de la enfermedad en el momento del screening.
7.Los pacientes que necesiten esteroides sistémicos deberían estar recibiendo ≤10 mg/día de prednisona (o equivalente) durante las dos semanas anteriores al inicio del tratamiento del estudio.
8.Los pacientes con otra neoplasia maligna primaria que no haya remitido durante como mínimo tres años a excepción de cáncer de piel no melanoma cáncer de próstata localizado tratado con intención curativa con antígeno específico de próstata no detectable, carcinoma cervical in situ en la biopsia o una lesión intraepitelial escamosa en el frotis de Papanicolaou (Pap) y cáncer de tiroides (excepto anaplásico).
9.Infecciones sistémicas activas que precisan antibióticos.
10.Infección activa conocida por el virus de la hepatitis A, B o C.
11.Diagnóstico conocido de infección por el virus de la inmunodeficiencia humana (VIH).
12.Mujeres embarazadas o lactantes.
13.Reacción anafiláctica anterior u otra reacción grave a la infusión asociada con la administración de anticuerpos humanos que no se pueda tratar con tratamiento sintomático habitual.
14.Presencia de enfermedad metastásica conocida del sistema nervioso central, meníngea o epidural. Con todo, se permite la inclusión de pacientes con metástasis cerebrales conocidas si han permanecido estables durante ≥ 4 semanas antes de la primera dosis del tratamiento del estudio. Se define estable como ausencia de síntomas neurológicos o que estén resueltos en el momento basal, sin indicios radiológicos de progresión y necesidad de esteroides de ≤10 mg/día de prednisona o equivalente.
15.Insuficiencia cardiaca o cardiopatía clínicamente significativa.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint family (see FDA Guidance for Industry, 2017) includes:
• OS, defined as the time to death from any cause measured from the date of randomization.
• ORR by blinded independent review using RECIST v1.1

La familia del criterio de valoración principal (véase la Guía para la Industria de la Administración estadounidense de Alimentos y Medicamentos [FDA] de 2017) incluye:
•SG, definida como el tiempo transcurrido desde la fecha randomización a la muerte por cualquier causa.
•TRG mediante revisión independiente enmascarada utilizando los Criterios RECIST v1.1

E.5.1.1

Timepoint(s) of evaluation of this end point

Tumor assessments will be performed at Screening and Week 12, then every 8 weeks for the first year and every 12 weeks during subsequent years.

Se efectuarán evaluaciones del tumor en el screening y en la semana 12, luego cada ocho semanas durante el primer año y cada doce semanas en los años siguientes

E.5.2

Secondary end point(s)

• ORR by blinded independent review using modified immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)
• ORR by investigator assessment using RECIST v1.1 and modified irRECIST
• Durable response rate (DRR) by blinded independent review and investigator assessment (using RECIST v1.1 and modified irRECIST), defined as the rate of CR or partial response (PR) lasting ≥6 months with onset during the first 12 months of treatment
• Time to response, defined as time to a complete or partial response (using RECIST v1.1 and modified irRECIST) measured from the date of randomization, by blinded independent review and investigator assessment
• Progression-free survival (PFS), defined as the time to disease progression or death from any cause measured from the date of randomization, by investigator assessment (using RECIST v1.1 and modified irRECIST)
• PFS, by investigator assessment (using RECIST v1.1 and modified irRECIST) and OS at 1 and 2 years
• PRO using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
• Safety, including AEs, laboratory and vital sign tests, electrocardiograms (ECGs), ECOG, and physical examination
• Plasma PK of IMO 2125

•TRG mediante revisión independiente enmascarada utilizando los Criterios de evaluación de respuesta en tumores sólidos inmunorrelacionados modificados (RECIST)
•TRG, evaluada por el investigador, usando los criterios RECIST v1.1 y los criterios RECISTir modificados
•Tasa de respuesta duradera (TRD) mediante revisión independiente enmascarada y evaluación del investigador (usando los criterios RECIST v1.1 y los criterios RECISTir modificados), definida como la tasa de RC o respuesta parcial (RP) que dure ≥6 meses con inicio durante los primeros doce meses de tratamiento.
•Tiempo hasta la respuesta, definido como el tiempo hasta los primeros indicios de respuesta completa o parcial (usando los criterios RECIST v1.1 y los criterios RECISTir modificados), medido desde la fecha de la randomización, mediante revisión independiente enmascarada y evaluación del investigador.
•Supervivencia libre de progresión (SLP), definida como el tiempo transcurrido hasta la progresión de la enfermedad o la muerte por cualquier causa determinada desde la fecha de la randomización mediante evaluación del investigador (usando los criterios RECIST v1.1 y los criterios RECISTir modificados).
•SLP, evaluada por el investigador (usando los criterios RECIST v1.1 y los criterios RECISTir modificados) y SG al año y a los dos años.
•RCP mediante el cuestionario de calidad de vida Core 30 de la Organización Europa para la Investigación y el Tratamiento del Cáncer (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, EORTC QLQ-C30)
•Seguridad, entre otros, AA, pruebas analíticas y de las constantes vitales, electrocardiogramas (ECG), ECOG y exploración física
•FC en plasma de IMO 2125

E.5.2.1

Timepoint(s) of evaluation of this end point

Various, refer to information in E.5.2.

Varios, ver la información en la sección E.5.2.

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

Yes

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

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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

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

Australia

Canada

Czech Republic

France

Germany

Italy

Netherlands

Spain

Sweden

United Kingdom

United States

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

The study is complete when 219 randomized subjects have died.

El estudio se dará por terminado cuando hayan muerto 219 pacientes

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:

140

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

168

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

188

F.4.2.2

In the whole clinical trial

308

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

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

2019-01-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-01-17

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2021-06-01

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