Clinical Trials Register

Summary
EudraCT Number:	2015-000471-27
Sponsor's Protocol Code Number:	CBYM338E2202E1
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:	2015-09-11
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

Spain - AEMPS

A.2

EudraCT number

2015-000471-27

A.3

Full title of the trial

A 28 week randomized withdrawal extension of a doubleblind, placebo-controlled, parallel group study to assess durability of effect on skeletal muscle strength and function upon withdrawal of bimagrumab 70, 210, 700 mg in older adults with sarcopenia

Estudio de extensión doble ciego, controlado con placebo, de grupos paralelos de 28 semanas de duración para evaluar la duración del efecto en la fuerza y la función musculares esqueléticas tras la retirada aleatorizada de bimagrumab 70, 210, 700 mg en adultos de edad avanzada con sarcopenia

A.3.1

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

Study to assess the effect of bimagrumab withdrawal in older adults with sarcopenia (low muscle mass and mobility).

Estudio para evaluar el efecto de la retirada de bimagrumab en adultos de edad avanzada con sarcopenia (baja masa y mobilidad muscular)

A.4.1

Sponsor's protocol code number

CBYM338E2202E1

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	Novartis Farmacéutica, S.A.
B.1.3.4	Country	Spain
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	Novartis Pharma Services AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Farmacéutica, S.A.
B.5.2	Functional name of contact point	Departamento Medico (ICRO)
B.5.3	Address:
B.5.3.1	Street Address	Gran Via de les Corts Catalanes, 764
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08013
B.5.3.4	Country	Spain
B.5.4	Telephone number	34900353036
B.5.5	Fax number	34932479903
B.5.6	E-mail	eecc.novartis@novartis.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	bimagrumab
D.3.2	Product code	BYM338
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	Bimagrumab
D.3.9.1	CAS number	1356922-05-8
D.3.9.2	Current sponsor code	BYM338
D.3.9.3	Other descriptive name	Anticuerpo Monoclonal Humano contra ActRII
D.3.9.4	EV Substance Code	SUB32641
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	150
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	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

Sarcopenia

E.1.1.1

Medical condition in easily understood language

Low muscle mass and gait speed in elderly subjects

Baja masa muscular y velocidad de la marcha en pacientes ancianos

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.0
E.1.2	Level	PT
E.1.2	Classification code	10063024
E.1.2	Term	Sarcopenia
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue 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

Assess the durability of effect of bimagrumab (BYM) by comparing withdrawal of BYM (i.e., BYM/placebo PBO switch) treatment with continued BYM administration every 4 weeks for 24 additional weeks of treatment (following participation in the core study) in older adults with sarcopenia as measured by change from week 25 to week 49 on the 6MWT

Evaluar la duración del efecto de bimagrumab (BYM) comparando la retirada del tratamiento con BYM (es decir, cambio de BYM/placebo [PBO]) con una administración continuada de BYM cada 4 semanas durante 24 semanas más de tratamiento (después de la participación en el estudio principal) en adultos de edad avanzada con sarcopenia según la medición del cambio desde la semana 25 hasta la semana 49 en la 6MWT.

E.2.2

Secondary objectives of the trial

- Evaluate the effect of BYM given intravenously every 4 weeks for 24 additional weeks of treatment (following completion of 24 weeks of treatment in the core study) on safety and tolerability as assessed by measures such as vital signs, clinical laboratory variables, electrocardiogram, echocardiogram, and adverse events as compared to treatment with PBO in older adults with sarcopenia
- Evaluate the durability of effect of BYM by comparing withdrawal of BYM (i.e. BYM/PBO switch) treatment with continued BYM administration every 4 weeks for 24 additional weeks of treatment
(following completion of 24 weeks of treatment in the core study) in older adults with sarcopenia as measured by change from week 25 to week 49 on: - performance on the Short Physical Performance Battery score mobility as measured in gait speed (GS
measured as a component of the SPPB) over 4 meters - total lean body mass and appendicular skeletal muscle index measured
by dual energy X-ray absorptiometry

? Evaluar el efecto de BYM administrado por vía intravenosa cada 4 semanas durante 24 semanas más de tratamiento (después de la participación en el estudio principal) en la seguridad y tolerabilidad mediante medidas como constantes vitales, variables clínicas de laboratorio, electrocardiograma, ecocardiografía y acontecimientos adversos en comparación con el tratamiento con PBO.
? Evaluar la duración del efecto de BYM comparando la retirada del tratamiento con BYM con una administración continuada de BYM cada 4 semanas durante 24 semanas más de tratamiento (después de la participación en el estudio principal) según la medición del cambio desde la semana 25 hasta la semana 49 en:
+ El rendimiento en la puntuación de la prueba de la serie abreviada de rendimiento físico.
+ La movilidad medida en la velocidad de la marcha (VM; medida como un componente de la SPPB) a lo largo de 4 metros.
+ La masa corporal magra total e índice muscular esquelético apendicular medidos por DEXA.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Men and postmenopausal women aged 70 years or older that have participated in, and have completed the full study treatment period per protocol (24 weeks/EOT visit) in the preceding core study (CBYM338E2202).

Other protocol-defined inclusion criteria may apply.

Hombres y mujeres postmenopáusicas ? 70 años de edad que hayan participado y hayan completado todo el periodo de tratamiento del estudio de acuerdo con el protocolo (24 semanas/visita de EOT) en el estudio principal anterior (CBYM338E2202).

Ver protcolo para mas detalle

E.4

Principal exclusion criteria

- Use of prohibited treatments as per recommendations outlined in protocol
- History of severe hypersensitivity reaction in the core study (CBYM338E2202)
- History of breaking of the blind (inadvertently or for emergency reasons) in the core study (CBYM338E2202)
- History of adverse event(s) in the core study (CBYM338E2202) that in the judgment of the investigator, taking into account the subject?s overall status, prevent the subject from entering the extension study
- Clinically significant abnormal liver function tests that would have resulted in discontinuation of study drug while participating in the core study (CBYM338E2202) as per protocol
- Any medical condition or laboratory finding, which, in the opinion of the investigator prevents the subject from continuing participation in the study, may interfere with participation in the study, might confound the results of the study, or pose an additional safety risk to the subject in administering bimagrumab
- Concurrent enrollment in a clinical trial involving an investigational drug or off- label use of a drug, or any other type of medical research judged to be scientifically or medically incompatible with this study (not including enrollment in BYM338E2202 core study).

- Uso de tratamientos prohibidos según las recomendaciones de la Tabla 5-1.
- Antecedentes de reacción de hipersensibilidad grave en el estudio principal.
- Antecedentes de desenmascaramiento (involuntariamente o por algún motivo urgente) en el estudio principal.
- Antecedentes de acontecimiento(s) adverso(s) en el estudio principal que según el criterio del investigador, teniendo en cuenta el estado general del sujeto, impidan que el sujeto participe en el estudio de extensión.
- Resultados anómalos clínicamente significativos de las pruebas de función hepática que habrían resultado en la retirada del fármaco del estudio durante la participación en el estudio principal de acuerdo con el protocolo (como se describe en el Anexo 1) como SGOT (AST), SGPT (ALT), fosfatasa alcalina o bilirrubina sérica (salvo enfermedad de Gilbert).
- Pacientes con cualquier enfermedad o hallazgo en las pruebas analíticas (p. ej., un resultado clínicamente significativo o sin motivo aparente en las pruebas analíticas) que, según el criterio del investigador, teniendo en cuenta el estado general del sujeto, impidan que el sujeto continúe participando en el estudio, pueda interferir en la participación en el estudio, pueda llevar a confusión en los resultados del estudio o suponer un riesgo de seguridad adicional para el sujeto al administrar bimagrumab.
- Participación concurrente en un ensayo clínico relacionado con un fármaco en investigación o uso de un fármaco en condiciones distintas a las autorizadas, o cualquier otro tipo de investigación médica considerada científica o médicamente incompatible con este estudio (sin incluir la inclusión en el estudio principal BYM338E2202).

E.5 End points

E.5.1

Primary end point(s)

6 minute walk test

Test de deambulación de 6 minutos

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 25, 49

Semana 25 y 49

E.5.2

Secondary end point(s)

- Safety and tolerability
- Short Physical Performance Battery
- Gait speed
- Total lean body mass and appendicular skeletal muscle index measured by DXA

- Seguridad y tolerabilidad
- Test de rendimiento fisico (SPPB)
- Velocidad de la marcha
- Masa corporal magra total e índice muscular esquelético apendicular medido por densitometria osea.

E.5.2.1

Timepoint(s) of evaluation of this end point

- Safety and tolerability: Weeks 25, 29, 37, 45, 49, 53
- Short Physical Performance Battery, Gait speed: Weeks 33, 41, 49
- Total lean body mass and appendicular skeletal muscle index measured by DXA: Weeks 37,49

- Seguridad y tolerabilidad: Semanas 25, 29, 37, 45, 49, 53
- Test de rendimiento fisico y velocidad de la marcha: Semanas 33, 41, 49
- Masa corporal magra total e índice muscular esquelético apendicular medido por densitometria osea: Semanas 37 y 49

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

Yes

E.6.13.1

Other scope of the trial description

Durability of effect of bimagrumab & tolerability

Durabilidad del efecto y tolerabilidad de bimagrumab

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

European Union

Japan

Switzerland

Taiwan

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

Ultima visita del ultimo paciente

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)

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

240

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

240

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

Ninguno

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

2015-10-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-10-05

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-12-03

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