Clinical Trials Register

Summary
EudraCT Number:	2011-005103-32
Sponsor's Protocol Code Number:	H9S-MC-JDCG
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-09-03
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2011-005103-32

A.3

Full title of the trial

Protocol H9S-MC-JDCG A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2/3 Study of LY2127399 in Combination with Bortezomib and Dexamethasone in Patients with Previously Treated Multiple Myeloma

studio di fase II/III, multicentrico, randomizzato, in doppio cieco controllato verso placebo, su LY2127399 in associazione con bortezomib e dexametasone in pazienti con mieloma multiplo gia' precedentemente trattato.

A.3.1

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

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2/3 Study of LY2127399 in Combination with Bortezomib and Dexamethasone in Patients with Previously Treated Multiple Myeloma

A.4.1

Sponsor's protocol code number

H9S-MC-JDCG

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	ELI LILLY
B.1.3.4	Country	Italy
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	ELI LILLY AND COMPANY
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	ELI LILLY
B.5.2	Functional name of contact point	CLINICA TRIAL INFORMATION
B.5.3	Address:
B.5.3.1	Street Address	CHEMIN DES COQUELICOTS 16
B.5.3.2	Town/ city	VERNIER/GENEVRE
B.5.3.3	Post code	1214
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	00441276483153
B.5.5	Fax number	00441276483378
B.5.6	E-mail	EU_Lilly_Clinical_Trials@lilly.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	Tabalumab
D.3.2	Product code	LY2127399
D.3.4	Pharmaceutical form	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.3.9.2	Current sponsor code	LY2127399
D.3.9.3	Other descriptive name	Tabaluman
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	100 to 300
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.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	VELCADE*EV 1FL 3,5MG 1MG/ML
D.2.1.1.2	Name of the Marketing Authorisation holder	JANSSEN CILAG SpA
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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.3.4	Pharmaceutical form	Powder for solution for injection
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.3.9.1	CAS number	179324-69-7
D.3.9.3	Other descriptive name	Bortezomib
D.3.9.4	EV Substance Code	SUB20020
D.3.10	Strength
D.3.10.1	Concentration unit	mg/m2 milligram(s)/square meter
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: 3
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	Dexamethason Acis
D.2.1.1.2	Name of the Marketing Authorisation holder	acis Arzneimittel GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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.3.4	Pharmaceutical form	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.3.9.1	CAS number	50-02-2
D.3.9.3	Other descriptive name	DEXAMETHASONE
D.3.9.4	EV Substance Code	SUB07017MIG
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	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.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

Previously Treated Multiple Myeloma

Mieloma Multiplo precedentemente trattato

E.1.1.1

Medical condition in easily understood language

Multiple Myeloma

Mieloma Multiplo

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	15.0
E.1.2	Level	PT
E.1.2	Classification code	10028228
E.1.2	Term	Multiple myeloma
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 Phase 2 is to select a dose of LY2127399 to assess with bortezomib and dexamethasone in Phase 3. The primary objective of Phase 3 is to compare PFS after treatment with the dose of LY2127399 selected in Phase 2, bortezomib, and dexamethasone, to that of placebo, bortezomib, and dexamethasone in patients with relapsed/refractory MM.

L'obiettivo primario della fase II è quello di scegliere una dose di LY2127399 da valutare in cosomministrazione con bortezomib e desametasone nella successiva fase III. La scelta della dose di LY2127399 da usare nella fase III sarà basata sull'analisi della qualità della risposta e sulla valutazione del profilo complessivo di sicurezza dei due bracci con dose differente. L'obiettivo primario della fase III consiste nel confrontare la PFS dopo il trattamento con LY2127399, nella dose selezionata tramite la fase II, bortezomib e desametasone, a quella raggiunta con placebo, bortezomib e desametasone in pazienti con MM recidivante/refrattario.

E.2.2

Secondary objectives of the trial

In addition to the primary objective of PFS, there will be 3 key secondary outcomes compared between treatments after the Phase 3 portion of the study, listed in order of precedence: • Overall survival (OS) • Time to first skeletal-related event (SRE) • The incidence of clinically significant pain response Additional secondary objectives for assessment at the end of the study (Section 4) are as follows: • To compare the following efficacy variables between the treatment arms: o Time to next treatment o Time to progression o Response rate and duration of response (if the study progresses to Phase 3) o Progression-free survival (PFS) (if study does not progress to Phase 3) • To describe the population PK of LY2127399 in patients with MM • To describe the immunogenicity of LY2127399 in patients with MM -Biomarker objectives - Health outcomes objectives

Oltre all'obiettivo primario riguardante la PFS,dopo la fase III dello studio i trattamenti saranno confrontati anche sulla base di 3 esiti secondari principali,elencati in ordine di precedenza:  Sopravvivenza globale (OS)  Tempo al primo evento correlato all'apparato scheletrico (SRE)  Incidenza di risposta algica clinicamente significativa Ulteriori obiettivi secondari per la valutazione al termine dello studio sono:  Confronto delle seguenti variabili di efficacia fra i bracci di trattamento o PFS (se lo studio viene interrotto dopo la fase II) o Tempo al successivo trattamento (TNT) o Tempo alla progressione (TTP) o Tasso e durata di risposta (se lo studio passa alla fase III)  Descrizione della popolazione farmacocinetica di LY2127399 nei pazienti con MM  Valutazione dell'immunogenicità di LY2127399 nei pazienti con MM

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Have symptomatic and/or progressive multiple myeloma that was previously treated with at least 1 and no more than 3 prior lines of therapy -Have measurable disease -Are ≥18 years of age -Have given written informed consent prior to any study-specific procedures -Have adequate organ function -Treatment with prior autologous transplant is permitted

i pazienti devono avere almeno 18 anni di età e presentare un MM attivo già trattato in precedenza con almeno una, ma non più di tre, linee di terapia pregresse. I pazienti devono presentare una malattia misurabile, un performance status di ≤2 secondo l'Eastern Cooperative Oncology Group, un'aspettativa di vita di ≥12 settimane e sufficiente funzionalità organica. Sono consentiti una precedente terapia con bortezomib e trapianto autologo pregresso

E.4

Principal exclusion criteria

Have had less than a minimal response or have had progressive disease within 60 days of most recent therapy with a proteasome inhibitor • -Plan to proceed to autologous transplant for consolidation after treatment on Study JDCG • -Have an active infection or ongoing treatment for systemic infection (''ongoing treatment'' does not include prophylactic anti-infectives), chest x-ray suggestive of tuberculosis, or history/risk of chronic/latent infection that may reactivate in the presence of study therapy • -Have positive test results for human immunodeficiency virus (HIV), evidence of hepatitis B (positive for hepatitis B surface antigen, or positive for hepatitis B core antibody and negative for hepatitis B surface antibody) or positive test results of hepatits C virus (HCV; positive for anti-hepatitis C antibody). A positive test for HCV is defined as a) positive for hepatitis C antibody (HepCAb), and b) confirmed positive via the hepatitis C recombinant immunoblot assay.-Prior allogeneic hematopoietic stem cell transplant

I pazienti non devono aver subito progressioni della malattia nei 60 giorni successivi alla più recente terapia con un inibitore del proteasoma o aver avuto una risposta meno che parziale a tale terapia. Inoltre i pazienti non devono avere un'infezione recente o in atto, essere positivi al test per l'HIV, presentare segni di epatite B o C attiva o essere affetti da neuropatia periferica di grado ≥2 o di qualsiasi grado se accompagnata da dolore (National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 [NCI-CTCAE v. 4.0], 2009)

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint of Phase 2 is to select a dose of LY2127399 The primary endpoint of Phase 3 is to compare PFS between the treatment arms

E.5.1.1

Timepoint(s) of evaluation of this end point

Phase 2 Primary Endpoint: 2 cycles after the last patient is enrolled to Phase 2 Phase 3 Primary Endpoint: at least 450 PFS events

Fase II: 2 cicli copo che l' ultimo paziente è arruolato nella fase II Fase III: almeno 450 eventi di PFS

E.5.2

Secondary end point(s)

Phase 3 secondary Endpoint: overall survival

fase III:sopravvivenza globale

E.5.2.1

Timepoint(s) of evaluation of this end point

382 deaths

382 decessi

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

Yes

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)

Yes

E.8.2.2

Placebo

Yes

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Desametasone, Bortexomib

Dexamethasone, Bortexomib

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

Brazil

Canada

Korea, Republic of

Mexico

Taiwan

Turkey

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

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

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

Number of subjects for this age range:

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

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

398

F.4.2.2

In the whole clinical trial

771

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)

Patients will receive study treatment until they require discontinuation of all study therapy.
After that pats will be treated according local medical practice and will continue to receive a follow up according protocol follow up procedures

i pazienti saranno trattati fino a quando non sarà necessario sospendere il trattamento.Dopodichè i pazienti sarannos eguiti secondo la locale pratica clinica e saranno seguiti come follow up come indicato dal protocollo .

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

2012-09-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-07-16

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-10-28

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials