Clinical Trials Register

Summary
EudraCT Number:	2019-000969-21
Sponsor's Protocol Code Number:	MG0004
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Restarted
Date on which this record was first entered in the EudraCT database:	2019-11-11
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

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2019-000969-21

A.3

Full title of the trial

A Randomized, Open-Label Extension Study to Investigate the Long-Term Safety, Tolerability, and Efficacy of Rozanolixizumab in Adult Patients With Generalized Myasthenia Gravis

Estudio de extensión, aleatorizado y abierto, para investigar la seguridad, tolerabilidad y eficacia a largo plazo de rozanolixizumab en pacientes adultos con miastenia gravis generalizada

A.3.1

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

A study to investigate the long-term safety, tolerability, and efficacy of rozanolixizumab in adult patients with generalized myasthenia gravis

Estudio para investigar la seguridad, tolerabilidad y eficacia a largo plazo de rozanolixizumab en pacientes adultos con miastenia gravis generalizada.

A.3.2

Name or abbreviated title of the trial where available

MycarinGstudy

A.4.1

Sponsor's protocol code number

MG0004

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	UCB Biopharma SPRL
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	UCB Biopharma SPRL
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	UCB BIOSCIENCES GmbH
B.5.2	Functional name of contact point	Clin Trial Reg & Results Disclosure
B.5.3	Address:
B.5.3.1	Street Address	Alfred-Nobel-Strasse 10
B.5.3.2	Town/ city	Monheim
B.5.3.3	Post code	40789
B.5.3.4	Country	Germany
B.5.6	E-mail	clinicaltrials@ucb.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	Rozanolixizumab
D.3.2	Product code	UCB7665
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	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	rozanolixizumab
D.3.9.1	CAS number	1584645-37-3
D.3.9.2	Current sponsor code	UCB7665
D.3.9.4	EV Substance Code	SUB166282
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	140
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

Generalized myasthenia gravis

Miastenia gravis generalizada

E.1.1.1

Medical condition in easily understood language

Myasthenia gravis is an autoimmune disease that causes weakness in your muscles; it is caused by a communication problem between nerves and muscles.

La Miastenia Gravis es una enfermedad autoimmune que causa debilidad en los músculos; esta causada por problemas de comunicación entre nervios y músculos.

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10028417
E.1.2	Term	Myasthenia gravis
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

Evaluate the long-term safety and tolerability of rozanolixizumab in study participants with generalized myasthenia gravis (MG)

Evaluar la seguridad y tolerabilidad a largo plazo de rozanolixizumab en sujetos con miastenia gravis generalizada (MG)

E.2.2

Secondary objectives of the trial

Evaluate the long-term efficacy of rozanolixizumab in study participants with generalized myasthenia gravis (MG)

Evaluar la eficacia a largo plazo de rozanolixizumab en sujetos con miastenia gravis generalizada (MG)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Participant must be >= 18 years of age at the time of signing the informed consent
- Participant was eligible for MG0003 [NCT03971422] at the time of enrollment into MG0003 and the participant either completed the Observation Period of MG0003 or required rescue therapy during the Observation Period of MG0003
- Body weight >35 kg at Visit 1
- Study participants may be male or female
- A male study participant must agree to use contraception
- Female study participants of childbearing potential must agree to use a highly effective method of birth control
- A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
a) Not a woman of childbearing potential (WOCBP) OR
b) A WOCBP who agrees to follow the contraceptive guidance

- El participante debe tener 18 años en el momento de firmar el consentimiento informado
- El participante era elegible para el estudio MG0003 [NCT03971422] en el momento que fue reclutado en el MG0003 y, o bien completó el período de observación del MG0003, o bien requirió terapia de rescate durante el período de observación del MG0003
- Peso corporal >35 kg en La Visita 1
- Los participantes del estudio pueden ser hombres o mujeres
- Los varones participantes de estudio deben aceptar usar métodos anticonceptivos
- Las mujeres participantes de estudio en edad fértil deben estar de acuerdo en utilizar un método anticonceptivo altamente eficaz
- Una mujer participante es elegible para participar si no está embarazada, no está amamantando, y se da al menos una de las siguientes condiciones:
a) No es una mujer en edad fértil ó
b) Es una mujer en edad fértil que acepta seguir la guía anticonceptiva

E.4

Principal exclusion criteria

- Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, if applicable, chest X-rays (posterior anterior and lateral), and TB testing by a positive (not indeterminate) QuantiFERON®-TB Gold test
- Participant has received a live vaccination within 8 weeks prior to the Baseline visit; or intends to have a live vaccination during the course of the study or within 8 weeks following the final dose of study medication
- Study participant has experienced hypersensitivity reaction after exposure to other antineonatal Fc receptor (FcRn) drugs
- Study participant with severe (defined as Grade 3 on the myasthenia gravis-activates of daily living (MG-ADL) scale) weakness affecting oropharyngeal or respiratory muscles, or who has myasthenic crisis or impending crisis
- Participant has absolute neutrophil count <1500 cells/mm3
- Participant has any laboratory abnormality that, in the opinion of the Investigator, is clinically significant, has not resolved at randomization, and could jeopardize or compromise the study participant’s ability to participate in this study
- Participant has 12-lead electrocardiogram (ECG) with findings considered to be clinically significant upon medical review. The clinical significance of the findings needs to be assessed by the Investigator to determine eligibility, and any queries regarding continuation of the study participant must be addressed with the Medical Monitor
- Study participant has renal impairment, defined as serum creatinine level of ≥1.4 mg/dL for females and ≥1.5mg/dL for males
- Study participant has >2x upper limit of normal (ULN) of any of the following at Visit 1: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). If study participant has elevations only in total bilirubin that are >ULN and <1.5xULN, fractionate bilirubin to identify possible undiagnosed Gilbert’s syndrome (ie, direct
bilirubin <35%). For randomized study participants with a baseline result >ULN for ALT, AST, ALP, or total bilirubin but <1.5xULN, a baseline diagnosis and/or the cause of any clinically meaningful elevation must be understood and recorded in the electronic Case Report form (eCRF). Tests that result in ALT, AST, or ALP up to 25% above the exclusion limit (>2xULN) may be repeated once for confirmation
- Study participant has positive human immunodeficiency virus antibody test
- Study participant met any mandatory withdrawal or mandatory study drug discontinuation criteria MG0003 [NCT03971422] or discontinued study medication in MG0003, with the exception of discontinuation due to a need for rescue treatment
- Study participant is not considered capable of adhering to the protocol visit schedule, or medication intake according to the judgment of the Investigator
- Study participant has a lifetime history of suicide attempt (including an active attempt, interrupted attempt, or aborted attempt), or had suicidal ideation since the last visit in MG0003 as indicated by a positive response (Yes) to either Question 4 or Question 5 of the ColumbiaSuicide Severity Rating Scale (C-SSRS) at Screening

- Evidencia de tuberculosis (TB) activa o latente documentada mediante historia clínica y examen, si procede, radiografías de tórax (anteroposterior y lateral) y pruebas de TB mediante una prueba de QuantiFERON®-TB Gold positiva (no indeterminada).
- El participante ha recibido una vacuna viva atenuada en las 8 semanas previas a la visita basal; o tiene la intención de recibir una vacuna viva atenuada en el trascurso del estudio o en las 8 semanas siguientes a la dosis final de la medicación del estudio.
- Participante del estudio que haya experimentado reacción de hipersensibilidad después de la exposición a otras drogas contra el receptor Fc neonatal (FcRn).
- Participante con debilidad grave (definida como grado 3 en la escala de actividades de la vida diaria en la miastenia gravis (AVD-MG)) que afecte a los músculos orofaríngeos o respiratorios, o con crisis miasténica o crisis inminente.
- El participante tiene un recuento absoluto de neutrófilos <1500 células/mm3
- El participante tiene cualquier anomalía de laboratorio que, en opinión del Investigador, sea clínicamente significativa, no se haya resuelto en la aleatorización, y pueda poner en peligro o comprometer la capacidad para participar en este estudio
- El participante tiene un electrocardiograma (ECG) de 12 derivaciones con hallazgos considerados clínicamente significativos tras la revisión médica. La importancia clínica de los hallazgos debe ser evaluada por el Investigador para determinar la elegibilidad, y cualquier pregunta con respecto a la continuación del participante del estudio debe ser abordada con el Monitor Médico
- El participante del estudio tiene insuficiencia renal, definida como un nivel sérico de creatinina >= 1,4 mg/dL para las mujeres y >=1,5 mg/dL para los hombres.
- El participante del estudio tiene >2x límite superior normal (ULN) de cualquiera de los siguientes en la Visita 1: alanina aminotransferasa (ALT), aspartato aminotransferasa (AST), fosfatasa alcalina (ALP), o bilirrubina >1.5xULN (se acepta un aumento puntual >1.5xULN si la bilirrubina está fraccionada y la bilirrubina directa <35%).
Si el participante del estudio tiene elevaciones sólo en la bilirrubina total que es >ULN y <1.5xULN, la bilirrubina fraccionada puede identificar un posible síndrome de Gilbert no diagnosticado (es decir, bilirrubina directa <35%).
Para los participantes del estudio aleatorizado con un resultado basal >ULN para ALT, AST, ALP, o bilirrubina total, pero <1.5xULN, un diagnóstico basal y / o la causa de cualquier elevación clínicamente significativa debe ser entendido y registrado en el cuaderno electrónico de recogida de datos (eCRF). Las pruebas que den como resultado ALT, AST o ALP hasta un 25% por encima del límite de exclusión (>2xULN) pueden repetirse una vez para su confirmación.
- El participante del estudio tiene una prueba positiva de anticuerpos del virus de la inmunodeficiencia humana.
- El participante en el estudio cumplió cualquier criterio de retirada o interrupción del medicamento del estudio MG0003 [NCT03971422] o discontinuó la medicación del estudio MG0003, a excepción de la interrupción por necesitar tratamiento de rescate.
- El participante del estudio no es considerado capaz de adherirse al calendario de visitas del protocolo, o tomar la medicación a juicio del Investigador.
- El participante del estudio tiene historial de intento de suicidio (incluyendo un intento activo, intento interrumpido o intento abortado), o tuvo ideas suicidas desde la última visita en el MG0003 como se indica en una respuesta positiva (Sí) a la pregunta 4 o a la pregunta 5 de la Escala Columbia para Evaluar el Riesgo de Suicidio (C-SSRS) durante la selección.

E.5 End points

E.5.1

Primary end point(s)

1. Percentage of participants with treatment-emergent adverse events (TEAEs)
2. Percentage of participants with treatment-emergent adverse events (TEAEs) leading to permanent withdrawal of study medication

1. Porcentaje de participantes con acontecimientos adversos surgidos durante el tratamiento (AAST).
2. Porcentaje de participantes con acontecimientos adversos surgidos durante el tratamiento (AAST) que provocan la retirada de la medicacion de estudio

E.5.1.1

Timepoint(s) of evaluation of this end point

1.+2.: From Baseline until Final Visit (up to Week 60)

1.+2.: Desde visita basal hasta visita final (hasta semana 60)

E.5.2

Secondary end point(s)

1. Change from Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) score at each scheduled assessment during Treatment and Observation Periods.
2. Change from Baseline in Myasthenia Gravis (MG)-Composite score at each scheduled assessment during Treatment and Observation Periods.
3. Change from Baseline in Quantitative Myasthenia Gravis (QMG) score at each scheduled assessment during Treatment and Observation Periods.
4. Percentage of participants using rescue medication (intravenous infusion of immunoglobulin G (IVIg) or plasma exchange (PEX)) during the study.

1. Cambio desde la visita basal en la puntuación de la escala de actividades de la vida diaria en la miastenia gravis (AVD-MG), en cada evaluación durante los periodos de tratamiento y observación.
2. Cambio desde la visita basal en la puntuación compuesta de miastenia gravis, en cada evaluación durante los periodos de tratamiento y observación.
3. Cambio desde la visita basal en la puntuación cuantitativa de la miastenia gravis (QMG) en cada evaluación durante los periodos de tratamiento y observación.
4. Porcentaje de pacientes que utilizan medicación de rescate (perfusión intravenosa de Inmunoglobulina G o plasmaféresis) durante el estudio.

E.5.2.1

Timepoint(s) of evaluation of this end point

1.-4.: From Baseline at each scheduled assessment during Treatment and Observation Periods (up to Week 60)

1.-4.: Desde la visita basal en cada evaluación durante los periodos de tratamiento y observación (hasta la semana 60)

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

Tolerability, Immunogenicity

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

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

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

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

Belgium

Canada

Czech Republic

Denmark

France

Germany

Hungary

Italy

Poland

Russian Federation

Spain

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

LVLS

Última visita del último 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

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.1.1.1

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:

216

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

110

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)

Eligible participants will be allowed receiving expanded access.

Los participantes elegibles podrán recibir un uso compasivo

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

2020-02-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-11-13

P. End of Trial
P.	End of Trial Status	Restarted

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