Clinical Trials Register

Summary
EudraCT Number:	2020-004997-23
Sponsor's Protocol Code Number:	BN42358
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:	2021-09-01
Trial 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

2020-004997-23

A.3

Full title of the trial

A PHASE IIB, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF INTRAVENOUS PRASINEZUMAB IN PARTICIPANTS WITH EARLY PARKINSON'S DISEASE

ESTUDIO EN FASE IIB, ALEATORIZADO, CON DOBLE ENMASCARAMIENTO, COMPARATIVO CON PLACEBO Y MULTICÉNTRICO, PARA EVALUAR LA EFICACIA Y LA
SEGURIDAD DE PRASINEZUMAB INTRAVENOSO EN PARTICIPANTES CON ENFERMEDAD DE PARKINSON INCIPIENTE

A.3.1

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

A Study to Evaluate the Efficacy and Safety of Intravenous Prasinezumab in Participants with Early Parkinson's Disease

Un estudio para evaluar la eficacia y seguridad del prasinezumab intravenoso en participantes con enfermedad de Parkinson temprana

A.4.1

Sponsor's protocol code number

BN42358

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	Roche Farma S. A. U. que realiza el ensayo en España y que actúa como representante F. Hoffmann-La Roche Ltd
B.1.3.4	Country	Switzerland
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	F. Hoffmann-La Roche Ltd
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	F. Hoffmann-La Roche Ltd
B.5.2	Functional name of contact point	Trial Information Support Line-TISL
B.5.3	Address:
B.5.3.1	Street Address	Grenzacherstrasse 124
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4070
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+349132557300
B.5.5	Fax number	+34913248196
B.5.6	E-mail	spain.start_up_unit@roche.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	aSyn Mab
D.3.2	Product code	RO7046015
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	Prasinezumab
D.3.9.2	Current sponsor code	RO7046015
D.3.9.3	Other descriptive name	PRX002, ELT2, anti-alpha-synuclein monoclonal antibody
D.3.9.4	EV Substance Code	SUB194018
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	180
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	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	Solution for injection/infusion
D.8.4	Route of administration of the placebo	Intravenous use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection/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

Early Parkinson's disease

Enfermedad de Parkinson incipiente

E.1.1.1

Medical condition in easily understood language

Parkinson's disease is a brain disorder that leads to shaking, stiffness, and difficulty with walking, balance, and coordination. Parkinson's symptoms usually begin gradually and get worse over time.

Parkinson es trastorno cerebral que provoca temblores,rigidezydificultad para caminar, mantener elequilibrio yla coordinación.Lossíntomas generalmente comienzan gradualmente y empeoran con eltiempo

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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10061536
E.1.2	Term	Parkinson's disease
E.1.2	System Organ Class	10029205 - Nervous system 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

To evaluate the efficacy of prasinezumab compared with placebo on basis of time to meaningful progression on motor signs of the disease

Evaluar la eficacia de prasinezumab en comparación con placebo basándose en el tiempo transcurrido hasta la progresión significativa de los signos motores de la enfermedad

E.2.2

Secondary objectives of the trial

• To evaluate the efficacy of prasinezumab compared with placebo on basis of time-to-worsening of patient’s motor function as reported by the patient and confirmed by the clinician, time to meaningful worsening in the overall disease as reported by the patient and by the clinician, change from baseline in motor function, change from baseline in bradykinesia and change from baseline in motor aspects of experiences of daily living
• To evaluate the safety of prasinezumab compared with placebo
• To characterize the prasinezumab pharmacokinetic (PK) profile
• To evaluate the immune response to prasinezumab

•Evaluar la eficacia de prasinezumab en comparación con placebo basándose en el tiempo transcurrido hasta el empeoramiento de la función motora percibido por el paciente y confirmado por el médico, tiempo hasta el empeoramiento significativo de la enfermedad en general según lo informado por el paciente y el médico, cambio desde el valor inicial en la función motora, cambio desde el valor inicial en la bradicinesia y cambio desde el valor inicial en los aspectos motores de las experiencias de la vida diaria.
•Evaluar la seguridad de prasinezumab en comparación con placebo.
•Caracterizar el perfil farmacocinético (PK) de prasinezumab
•Evaluar la respuesta inmune al prasinezumab

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Age >=50-85 years at time of signing the Informed Consent Form
• Diagnosis of idiopathic Parkinson's disease (PD) based on Movement disorder society (MDS) criteria with bradykinesia plus one of the other cardinal signs of PD (resting tremor, rigidity), without any other known or suspected cause of parkinsonism
• On symptomatic PD medication for at least 6 months, with stable doses for 3 months prior to baseline
• A diagnosis of PD for at least 6 months to maximum 3 years at screening
• Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part IV score= 0
• Hoehn and Yahr (H&Y) Stage I or II in ON and OFF states
• Dopamine transporter imaging with single photon emission computed tomography (DaT-SPECT) imaging consistent with dopamine transporter deficit, as assessed by the central reader
• No anticipated changes in PD medication from baseline throughout the study duration based on clinical status during screening
• Willingness and ability to use a smartphone application to measure PD-related symptoms for the duration of the study
• Willingness and ability to wear a smartwatch to measure PD-related motor signs

• Tener entre 50 y 85 años de edad en el momento de firmar el documento de consentimiento informado
• Tener un diagnóstico de EP idiopática según los criterios del MDS, con bradicinesia más uno de los otros signos cardinales de EP (temblor de reposo, rigidez), y sin ninguna otra causa conocida o presunta de parkinsonismo
• Con medicación para la EP sintomática durante al menos 6 meses, con dosis estables durante 3 meses antes del inicio
• Haber recibido el diagnóstico de EP entre 6 meses y 3 años antes, como máximo, de la selección.
• Tener una puntuación en la parte IV de MDS-UPDRS = 0.
• Encontrarse en estadio I o II de Hoehn y Yahr en estados ON y OFF
• Tener una (DaT-SPECT) compatible con déficit de transportadores de dopamina, evaluada por el evaluador central
• No tener previstas modificaciones de la medicación para la EP con respecto inicio en todo el
estudio, de acuerdo con el estado clínico durante la selección.
• Estar dispuesto y ser capaz de utilizar una aplicación de teléfono móvil para medir los
síntomas relacionados con la EP durante todo el estudio
• Estar dispuesto y ser capaz de llevar un reloj inteligente para medir los signos motores
relacionados con la EP

E.4

Principal exclusion criteria

• Medical history indicating a Parkinsonian syndrome other than idiopathic PD
• Diagnosis of PD dementia
• Diagnosis of a significant central nervous system (CNS) disease other than Parkinson’s disease
• Within the last year, unstable or clinically significant cardiovascular disease
• Uncontrolled hypertension
• Drug and/or alcohol abuse within 12 months prior to screening, in the investigator's judgment (Nicotine is allowed, Marijuana use is not allowed)
• Clinically significant abnormalities in laboratory test results at the screening visit, including hepatic and renal panels, complete blood count, chemistry panel and urinalysis
• Allergy to any of the components of prasinezumab, a known hypersensitivity, or a previous IRR following administration of any other monoclonal antibody
• Any contraindications to obtaining a brain MRI
• Any contraindications to DaT-SPECT imaging

• Antecedentes médicos indicativos de síndrome parkinsoniano distinto de la EP idiopática.
• Diagnóstico de demencia por EP.
• Diagnóstico de una enfermedad importante del sistema nervioso central distinta de la EP
• En el último año, enfermedad cardiovascular inestable o de trascendencia clínica
• Hipertensión no controlada
• Toxicomanía o alcoholismo en los 12 meses previos a la selección, según el criterio del investigador (Se permite el consumo de nicotina, No se permite el consumo de marihuana).
• Anomalías clínicamente significativas en los resultados de las pruebas de laboratorio en la visita de selección, incluidos paneles hepáticos y renales, hemograma completo, panel químico y análisis de orina.
• Alergia a cualquiera de los componentes de prasinezumab, hipersensibilidad conocida o RRP previa después de la administración de cualquier otro anticuerpo monoclonal
• Cualquier contraindicación para obtener una resonancia magnética cerebral.
• Cualquier contraindicación para la obtención de imágenes DaT-SPECT

E.5 End points

E.5.1

Primary end point(s)

Time to meaningful progression on motor signs of the disease, as assessed by >5 points increase in MDS-UPDRS Part III score from baseline

Tiempo hasta la progresión significativa de los signos motores de la enfermedad, según la evaluación de un aumento de> 5 puntos en la puntuación MDS-UPDRS Parte III desde el inicio

E.5.1.1

Timepoint(s) of evaluation of this end point

Throughout the study

Durante todo el estudio

E.5.2

Secondary end point(s)

1. Time-to-worsening of patient’s motor function as reported by the patient in MDS-UPDRS Part II and confirmed by the clinician in MDS-UPDRS Part III
2. Time to meaningful worsening in Patient Global Impression of Change (PGI-C, Overall Disease Subscale)
3. Time to meaningful worsening in Clinician Global Impression of Change (CGI-C, Overall Disease Subscale)
4. Change in motor function from baseline to Week 76, as measured by the MDS-UPDRS Part III total score
5. Change in bradykinesia from baseline to Week 76, as measured by the MDS-UPDRS Part III bradykinesia subscore
6. Change in motor aspects of experiences of daily living from baseline to Week 76, as measured by MDS-UPDRS Part II
7. Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
8. Incidence of adverse events of special interest
9. Incidence of treatment discontinuation due to adverse events
10. Incidence and severity of infusion-related reactions (IRRs)
11. Change from baseline in vital signs
12. Incidence of abnormal vital sign measurements
13. Change from baseline in electrocardiogram (ECG) assessments
14. Incidence of abnormal ECG assessments
15. Change from baseline in laboratory measurements
16. Incidence of abnormal laboratory measurements
17. Incidence of physical and neurologic examination abnormalities
18. Change from baseline in suicidal ideation, as measured by the Columbia-Suicide Severity Rating Scale (C-SSRS)
19. Serum concentration of prasinezumab at specified timepoints
20. Prevalence of anti-drug antibodies (ADAs) against prasinezumab at baseline
21. Incidence of ADAs against prasinezumab during the study

1.Tiempo hasta el empeoramiento de la función motora del paciente según lo informado por el paciente en MDS-UPDRS Parte II y confirmado por el médico en MDS-UPDRS Parte III
2. Tiempo transcurrido hasta un empeoramiento significativo en la Impresión global del paciente Cambio (PGI-C, subescala de enfermedad global).
3. Tiempo transcurrido hasta un empeoramiento significativo en la Impresión global del cambio por el médico (CGI-C, subescala de enfermedad global).
4. Variación de la función motora entre el inicio y la semana 76, determinada mediante la puntuación total de la parte III de la escala MDS-UPDRS.
5. Variación de la bradicinesia entre el inicio y la semana 76, determinada mediante la subpuntuación de bradicinesia de la parte III de la escala MDS-UPDRS
6. Variación de los aspectos motores de las experiencias cotidianas entre el inicio y la semana 76, evaluados mediante la parte II de la escala MDS-UPDRS.
7. Naturaleza, incidencia e intensidad de los acontecimientos adversos, con determinación de la intensidad según los criterios NCI-CTCAE v5.0.
8. Incidencia de acontecimientos adversos de interés especial.
9. Incidencia de las suspensiones del tratamiento por acontecimientos adversos.
10. Naturaleza, incidencia, gravedad, intensidad y cronología de las RRI.
11. Variación media de las constantes vitales con respecto al inicio
12. incidencia de mediciones anómalas de las constantes vitales
13. Variación de las evaluaciones electrocardiográficas a lo largo del tiempo con respecto inicio
14. Incidence of abnormal ECG assessments
15. Change from baseline in laboratory measurements
16. incidencia de evaluaciones electrocardiográficas anómalas.
17. Incidencia de anomalías en la exploración física y neurológica.
18 Variación con respecto inicio de las ideas suicidas, determinadas mediante la C-SSRS
19. Concentración sérica de prasinezumab en momentos específicos
20. Prevalencia de anticuerpos antidrogas (ADA) contra prasinezumab al inicio del estudio
21. Incidencia de ADA contra prasinezumab durante el estudio

E.5.2.1

Timepoint(s) of evaluation of this end point

1-3. Throughout the study
4-6. Baseline (Day 0) to 76 weeks
7-10. Up to end of study visit
11. Baseline to end of study visit
12. Up to end of study visit
13. Baseline to end of study visit
14. Up to end of study visit
15. Baseline to end of study visit
16-17. Up to end of study visit
18. Baseline end of study visit
19. At weeks 1, 2, 4, 8, 12, 24, 36, 52, 64, 76 and after week 76 every 12 weeks until the end of the study. 20. At Baseline
21. Up to end of study visit

1-3. Durante todo el estudio
4-6. Línea de base (día 0) a 76 semanas
7-10. Hasta el final de la visita de estudio
11. Desde el inicio hasta el final de la visita del estudio
12. Hasta el final de la visita de estudio
13. Desde el inicio hasta el final de la visita del estudio
14. Hasta el final de la visita del estudio
15. Desde el inicio hasta el final de la visita del estudio
16-17. Hasta el final de la visita de estudio
18. Visita de referencia al final del estudio
19. En las semanas 1, 2, 4, 8, 12, 24, 36, 52, 64, 76 y después de la semana 76 cada 12 semanas hasta el final del estudio. 20. Al inicio
21. Hasta el final de la visita de estudio

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

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

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

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

Canada

United States

Austria

France

Italy

Poland

Spain

United Kingdom

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

Last Patient Last Visit

Último paciente Última visita

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)

Yes

F.1.2.1

Number of subjects for this age range:

259

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

316

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

319

F.4.2.2

In the whole clinical trial

575

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)

N/A

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

2021-05-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-03-30

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

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