Clinical Trials Register

Summary
EudraCT Number:	2011-001735-22
Sponsor's Protocol Code Number:	CNTO328SMM2001
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-10-03
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

2011-001735-22

A.3

Full title of the trial

A Phase 2, Randomized, Double-blind, Placebo-controlled, Multicenter Study of Siltuximab (Anti IL 6 Monoclonal Antibody) in Subjects with High-risk Smoldering Multiple Myeloma

Estudio fase 2, aleatorizado, ciego, controlado con placebo y multicentrico de siltuximab (anticuerpo monoclonal anti-IL-6) en sujetos con Mieloma Múltiple Quiescente de alto riesgo

A.3.1

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

A Study of Siltuximab (Anti- IL 6 Monoclonal Antibody) in Patients with High-risk Smoldering Multiple Myeloma

Ensayo de Siltuximab (Anticuerpo monoclonal Anti-IL6) en pacientes con mieloma múltiple quiescente de alto riesgo

A.4.1

Sponsor's protocol code number

CNTO328SMM2001

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	Janssen-Cilag International N.V.
B.1.3.4	Country	Belgium
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	Janssen Research & Development
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	Janssen-Cilag International N.V.
B.5.2	Functional name of contact point	Clinical Registry Group
B.5.3	Address:
B.5.3.1	Street Address	Janssen Biologics BV - Clinical Registry Group, Archimedesweg 29
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	2333CM
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	31 071 524 21 66
B.5.5	Fax number	31 071 524 21 10
B.5.6	E-mail	ClinicalTrialsEU@its.jnj.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	Siltuximab
D.3.2	Product code	CNTO 328
D.3.4	Pharmaceutical form	Powder 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	Siltuximab
D.3.9.2	Current sponsor code	CNTO328
D.3.9.3	Other descriptive name	anti-IL-6 quimérica murina humana
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	400
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	Yes
D.3.11.13.1	Other medicinal product type	Anticuerpo monoclonal

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	Powder 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

High-risk Smoldering Multiple Myeloma

Mieloma Múltiple quiescente de alto riesgo

E.1.1.1

Medical condition in easily understood language

Smoldering Multiple Myeloma

Mileoma Múltiple Quiescente

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	LLT
E.1.2	Classification code	10028233
E.1.2	Term	Multiple myeloma without mention of remission
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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 demonstrate that siltuximab will delay progression of high-risk SMM as measured by the 1 year progression-free survival (PFS) rate.

El objetivo principal del estudio es demostrar que el siltuximab retardará la progresión del MMQ de alto riesgo, medida por la tasa de supervivencia libre de progresión (SLP) al año.

E.2.2

Secondary objectives of the trial

The secondary objectives of the study are to evaluate additional efficacy measurements including PFS and patient-reported symptoms (patient-reported outcomes [PROs]), as well as safety, pharmacokinetics, antibodies to siltuximab (immunogenicity), and potential biomarkers predictive of response to siltuximab treatment and progression to symptomatic multiple myeloma. Upon progression to multiple myeloma, cytogenetics and response to first subsequent multiple myeloma treatment will be characterized. During an interim analysis, the 6 month progressive disease indicator rate and other endpoints will be evaluated.

Los objetivos secundarios del estudio son evaluar medidas de eficacia adicionales, incluidas la SLP y los síntomas comunicados por los pacientes (resultados comunicados por los pacientes [RCP]), así como la seguridad, la farmacocinética, los anticuerpos contra el siltuximab (inmunogenicidad) y los posibles biomarcadores predictivos de la respuesta al tratamiento de siltuximab y la progresión a mieloma múltiple sintomático. Cuando se produzca progresión a mieloma múltiple, se caracterizarán la citogenética y la respuesta al primer tratamiento del mieloma múltiple posterior. Durante un análisis intermedio se evaluarán la tasa indicadora de progresión de la enfermedad a los 6 meses y otros criterios de valoración

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Diagnosis of SMM for < 4 years and a diagnosis of high-risk SMM
2. Patients must be within certain limits for protocol-specified laboratory tests
3. Eastern Cooperative Oncology Group Performance Status score of 0 or 1
4. Women of childbearing potential must agree to use adequate birth control measures during the study and for 3 months after receiving the last dose of study agent, and must have a negative pregnancy test at screening
5. Men must agree to use a double-barrier method of birth control and to not donate sperm during the study and for 3 months after receiving the last dose of study agent.

1. Diagnóstico de MMQ durante < 4 añosy diagnóstico de MMQ de alto riesgo.
2. El sujeto deberá cumplir ciertos limites de resultados de laboratorio especificados en el protocolo.
3. Estado funcional ECOG de 0 ó 1 (véase el apéndice 1)
4. Las mujeres en edad fértil deberán comprometerse a utilizar métodos anticonceptivos adecuados durante el estudio y en los 3 meses siguientes a la última dosis de fármaco del estudio, y deberán tener un resultado negativo en una prueba de embarazo (gonadotropina coriónica humana beta [?-HCG] en suero u orina) en la selección.
5. Los varones deberán comprometerse a utilizar un método anticonceptivo de doble barrera y a no donar semen durante el estudio y en los 3 meses siguientes a la última dosis de fármaco del estudio.

E.4

Principal exclusion criteria

1. Having symptomatic multiple myeloma, defined by any of the following (if due to myeloma): lytic bone lesions, severe osteopenia (low bone density), pathologic fractures, hypercalcemia (too much calcium in the blood), kidney insufficiency,
symptomatic hyperviscosity of the blood, or recurrent serious bacterial infections such as pneumonia
2. Primary systemic AL amyloidosis (a build-up of amyloid light chain proteins in the blood)
3. Prior or concurrent exposure to approved or investigational multiple myeloma treatments (Concurrent treatment with bone-protecting agents (eg, bisphosphonates, denosumab), or steroids are only allowed if given in a stable dose and for a nonmalignant condition. Concurrent treatment with erythropoietin-stimulating agents (ESAs) are not allowed.)
4. Prior exposure to agents targeting interleukin 6 (IL 6) or the IL 6 receptor
5. Other malignancy within the past 3 years, except for the following, if treated and not active: basal cell or nonmetastatic (non-spreading) squamous cell carcinoma of the skin, cervical carcinoma or International Federation of Gynecology and Obstetrics Stage 1 carcinoma of the cervix

1. Mieloma múltiple sintomático, definido por cualquiera de los siguientes (si se deben al mieloma):
a. Lesiones óseas líticas, osteopenia grave o fracturas patológicas
b. Hipercalcemia (calcio sérico corregido > 11,5 mg/dl)
c. Insuficiencia renal (creatinina > 2 mg/dl)
d. Otros: hiperviscosidad sintomática, infecciones bacterianas graves recurrentes como neumonía
2. Amiloidosis LA primaria sistémica
3. Exposición previa o concurrente a tratamientos para el mieloma múltiple aprobados o en investigación. Sólo se permite el tratamiento concomitante con fármacos osteoprotectores (p. ej., bisfosfonatos, denosumab) o esteroides si se administran en dosis estable para un proceso no maligno. No se permite el tratamiento concomitante con agentes estimuladores de la eritropoyesis (AEE)
4. Exposición previa a fármacos dirigidos a la IL-6 o al receptor de la IL-6
5. Otro tumor maligno en los últimos 3 años, a excepción de los siguientes si se han tratado y no están activos: carcinoma basocelular o escamocelular no metastásico de la piel, carcinoma cervical in situ o carcinoma de cérvix en estadio 1 de la Federación Internacional de Ginecología y Obstetricia (FIGO)

E.5 End points

E.5.1

Primary end point(s)

One-year progression-free survival rate (PFS)

Supervivencia Libre de Progresión al año (SLP)

E.5.1.1

Timepoint(s) of evaluation of this end point

One year after randomization of last patient

Un año después de la aleatorización del último paciente

E.5.2

Secondary end point(s)

1. Progression-free survivial (PFS)
2. European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Core 30 (EORTC QLQ C30)
3. Brief Pain Inventory (worst pain item)
4. Adverse events
5. Clinical laboratory evaluations
6. PD indicator rate
7. Overall survival

1. Supervivencia Libre de Progresión (SLP)
2. European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Core 30 (EORTC QLQ C30)
3. Brief Pain Inventory (apartado de peor dolor)
4. Eventos Adversos
5. Evaluaciones Clínicas de Laboratorio
6. Tasa indicadora de progresión
7. Supervivencia Global

E.5.2.1

Timepoint(s) of evaluation of this end point

1. Up to approximately 4 years after randomization of last patient
2. Up to approximately 4 years after randomization of last patient
3. Up to approximately 4 years after randomization of last patient
4. Up to approximately 4 years after randomization of last patient
5. Up to approximately 4 years after randomization of last patient
6. 6 months after randomization of last patient
7. Approximately 4 years after randomization of last patient

1. hasta aproximadamente 4 años después de la aleatorización del último paciente.
2. hasta aproximadamente 4 años después de la aleatorización del último paciente.
3. hasta aproximadamente 4 años después de la aleatorización del último paciente.
4. hasta aproximadamente 4 años después de la aleatorización del último paciente.
5. hasta aproximadamente 4 años después de la aleatorización del último paciente.
6. 6 meses después de la aleatorización del último paciente.
7. Aproximadamente 4 años después de la aleatorización del último paciente.

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

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

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

Australia

Belgium

France

Germany

Greece

Israel

Korea, Republic of

Spain

Sweden

United Kingdom

United States

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

The study will end approximately 4 years after randomization of the last subject or when the sponsor decides to stop the study, and include the End of Treatment Visit 4 weeks after the last study agent administration.

El estudio finalizará aproximadamente 4 años después de la aleatorización del último paciente o cuando el promotor decida parar el estudio, e incluir la visita de Fin de tratamiento 4 semanas después de la última administración del agente en estudio

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