Clinical Trials Register

Summary
EudraCT Number:	2022-000747-77
Sponsor's Protocol Code Number:	283PD302
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2022-09-19
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2022-000747-77

A.3

Full title of the trial

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Determine the Efficacy and Safety of BIIB122/DNL151 in Participants with Parkinson’s Disease and Pathogenic LRRK2 Variants

Studio di fase 3, multicentrico, randomizzato, in doppio cieco, controllato con placebo per determinare l’efficacia e la sicurezza di BIIB122/DNL151 in partecipanti con malattia di Parkinson e varianti patogene di LRRK2

A.3.1

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

A Study to Assess if BIIB122 Tablets are Safe and can Slow Worsening of Early-Stage Parkinson's Disease in Participants with Specific LRRK2 Genetic Variants Between the Ages of 30 and 80 Using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale

Uno studio per valutare se le compresse BIIB122 sono sicure e possono rallentare il peggioramento della malattia di Parkinson in fase iniziale nei partecipanti con specifiche varianti genetiche LRRK2 di età compresa tra 30 e 80 anni utilizzando la scala unificata di valutazione della malattia di Parkinson sponsorizzata dalla società per i disturbi del movimento (Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale, MDS-UPDRS)

A.3.2

Name or abbreviated title of the trial where available

LIGHTHOUSE

A.4.1

Sponsor's protocol code number

283PD302

A.5.4

Other Identifiers

Name:

IND/IDE Number:

Number:

135743

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	BIOGEN IDEC RESEARCH LIMITED
B.1.3.4	Country	United Kingdom
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	Biogen Idec Research Limited
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	Biogen Idec Research Limited
B.5.2	Functional name of contact point	N/A
B.5.3	Address:
B.5.3.1	Street Address	Innovation House, 70 Norden Road
B.5.3.2	Town/ city	Maidenhead, Berkshire
B.5.3.3	Post code	SL6 4AY
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	0000000
B.5.5	Fax number	0000000
B.5.6	E-mail	clinicaltrials@biogen.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	BIIB122
D.3.2	Product code	[DNL151]
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	2170179-24-3
D.3.9.2	Current sponsor code	BIIB122
D.3.9.3	Other descriptive name	DNL151, DN0001575, DN1575
D.3.9.4	EV Substance Code	SUB221129
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	75
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Parkinson's Disease

Morbo di Parkinson

E.1.1.1

Medical condition in easily understood language

Parkinson's Disease

Morbo di Parkinson

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 BIIB122 225 mg compared with placebo, based on the time to confirmed worsening in MDS-UPDRS Parts II and III combined score

Valutare l’efficacia di BIIB122 225 mg rispetto al placebo, in base al tempo al peggioramento confermato nel punteggio combinato delle Parti II e III della Scala di valutazione della malattia di Parkinson unificata della Società per i disturbi del movimento (MDS-UPDRS)

E.2.2

Secondary objectives of the trial

- To evaluate the safety and tolerability of BIIB122 225 mg compared with placebo when administered for 96 to 180 weeks
- To evaluate the efficacy of BIIB122 225 mg compared with placebo, based on the time to confirmed worsening in MDS-UPDRS Part II score
- To evaluate the efficacy of BIIB122 225 mg compared with placebo, based on change in the MDS-UPDRS Parts II and III combined score, when administered for 96 weeks
- To evaluate the efficacy of BIIB122 225 mg compared with placebo, based on change in SE-ADL score
- To evaluate the efficacy of BIIB122 225 mg compared with placebo, based on change in MDS-UPDRS Parts I, II, and III combined score

Valutare la sicurezza e la tollerabilità di BIIB122 225 mg rispetto al placebo quando somministrato per 96-180 settimane
- Valutare l’efficacia di BIIB122 225 mg rispetto al placebo, in base al tempo al peggioramento confermato nel punteggio della Parte II della scala MDS-UPDRS
- Valutare l’efficacia di BIIB122 225 mg rispetto al placebo, in base alla variazione nel punteggio combinato delle Parti II e III della scala MDS-UPDRS, quando somministrato per 96 settimane
- Valutare l’efficacia di BIIB122 225 mg rispetto al placebo, in base alla variazione nel punteggio Scala per la valutazione delle attività quotidiane di Schwab ed England (SE-ADL)
- Valutare l’efficacia di BIIB122 225 mg rispetto al placebo, in base alla variazione nel punteggio combinato delle Parti I, II e III della scala MDS-UPDRS

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Other types of substudies
Specify title, date and version of each substudy with relative objectives: Two biomarker substudies, a biofluid substudy and an imaging substudy,
may be conducted to evaluate exploratory biofluid and imaging
biomarkers in a subset of participants.
The objective of the biofluid substudy is to evaluate the change in
central and peripheral biomarkers over time. Collection will include LPs
for CSF collection and blood sampling. All biofluid substudy participants
are planned to participate in the CSF portion of the substudy. A subset of
those participants is planned to participate in the PBMC portion of the
substudy. Samples will be evaluated for measures of LRRK2 pathway,
lysosomal function, and exploratory measures relevant to PD.
The objective of the imaging substudy is to quantify changes in nigralstriatal
dopaminergic integrity over time using PET and MRI. The
substudy will be conducted with participants who are willing and able to
travel to central imaging facilities from participating study sites. Theoverall screening window will be increased by 7 days to a maximum of
42 days for participants in the imaging substudy to allow enough time to
complete assessments. Study site participation will be based on PET
radiotracer availability and site geography, at the discretion of the
Sponsor. PET imaging will use the 18F-AV133 radioligand that binds
VMAT-2. MRI may include, and not be limited to structural,
neuromelanin-sensitive, and susceptibility-weighted MRI sequences (to
be detailed in the Imaging/MRI Manual) to allow PET quantification and
evaluation of exploratory MRI biomarkers.
Participation in either substudy is optional for participants, where
approved per local regulations. All participants who opt to participate in
either of the substudies must provide additional written, informed
consent. Participation in a substudy is optional and does not exclude
participation in the other substudy.
The diagnostic imaging substudy will not be conducted in Italy.

Altre tipologie di sottostudi
specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: Potranno essere condotti due sottostudi sui biomarcatori (un sottostudio sui biofluidi e un sottostudio di diagnostica per immagini) per valutare i biomarcatori esplorativi dei biofluidi e della diagnostica per immagini in un sottogruppo di partecipanti.
L’obiettivo del sottostudio sui biofluidi è valutare la variazione nei biomarcatori centrali e periferici nel tempo. Il prelievo includerà le punture lombari (PL) per il prelievo di liquido cerebrospinale (LCS) e il prelievo di sangue. Si prevede che tutti i partecipanti al sottostudio sui biofluidi partecipino alla porzione di LCS del sottostudio. Si prevede che un sottogruppo di tali partecipanti partecipino alla porzione del prelievo di cellule mononucleate da sangue periferico (PBMC) del sottostudio. I campioni saranno valutati per le misure del pathway di LRRK2, la funzione lisosomiale e le misure esplorative rilevanti per la malattia di Parkinson (MP).
L’obiettivo del sottostudio di diagnostica per immagini è quantificare le variazioni nell’integrità dopaminergica nigro-striatale nel tempo utilizzando la tomografia ad emissione di positroni (PET) e la risonanza magnetica (RM). Il sottostudio sarà condotto con i partecipanti che sono disposti e in grado di recarsi presso le strutture di diagnostica per immagini centrali dai centri dello studio partecipanti. La finestra complessiva dello screening sarà aumentata di 7 giorni fino a un massimo di 42 giorni per i partecipanti al sottostudio di diagnostica per immagini, per consentire un tempo sufficiente per completare le valutazioni. La partecipazione dei centri dello studio si baserà sulla disponibilità di radiotraccianti PET e sull’area geografica del centro, a discrezione dello sponsor. La PET utilizzerà il radioligando 18F-AV133 che si lega al trasportatore vescicolare delle monoamine 2 (VMAT-2). La RM può includere, a titolo esemplificativo ma non esaustivo, sequenze di RM strutturali, sensibili alla neuromelanina e pesate in suscettibilità (da indicare in dettaglio nel Manuale di diagnostica per immagini/RM), per consentire la quantificazione della PET e la valutazione di biomarcatori RM esplorativi.
La partecipazione a uno dei due sottostudi è facoltativa per i partecipanti, ove approvata in base alle normative locali. Tutti i partecipanti che scelgono di partecipare a uno dei sottostudi devono fornire un ulteriore consenso informato scritto. La partecipazione a un sottostudio è facoltativa e non esclude la partecipazione all’altro sottostudio.
In Italia non verrà condotto il sottostudio di diagnostica per immagini.

E.3

Principal inclusion criteria

Key Inclusion Criteria:
- Clinical diagnosis of PD meeting the Movement Disorder Society Clinical Diagnostic Criteria within 5 years of the Screening Visit, inclusive, and at least 30 years of age at the time of diagnosis
- Modified Hoehn and Yahr scale, Stages 1 to 2.5 (in OFF state), inclusive, at Screening
- MDS-UPDRS Parts II and III (in OFF state) combined score =40 at Screening
- Screening genetic test results verifying the presence of a pathogenic leucine-rich repeat kinase 2 (LRRK2) variant

- Diagnosi clinica di MP che soddisfi i criteri di diagnostica clinica della Società per i disturbi del movimento entro 5 anni dalla visita di screening, incluso, e avente almeno 30 anni di età al momento della diagnosi
- Stadio da 1 a 2,5 (inclusi) della scala di Hoehn e Yahr modificata (in stato OFF), allo screening
- Punteggio combinato delle Parti II e III della scala MDS-UPDRS (in stato OFF) =40 allo screening
- Risultati dei test genetici di screening che accertano la presenza di una variante patogena della chinasi ripetuta 2 ricca di leucine (LRRK2)

E.4

Principal exclusion criteria

Key Exclusion Criteria:
- Clinically significant neurologic disorder other than PD, including, but not limited to, stroke, dementia, or seizure within 5 years of Screening Visit, in the opinion of the Investigator
- Clinical evidence of atypical parkinsonism (e.g., multiple-system atrophy or progressive supranuclear palsy) or evidence of drug-induced parkinsonism

- Disturbo neurologico clinicamente significativo diverso dalla MP, compresi, a titolo esemplificativo ma non esaustivo, ictus, demenza o crisi convulsive, entro 5 anni dalla visita di screening, a giudizio dello sperimentatore
- Evidenza clinica di parkinsonismo atipico (ad es., atrofia multisistemica o paralisi sopranucleare progressiva) o evidenza di parkinsonismo farmaco-indotto

E.5 End points

E.5.1

Primary end point(s)

Time to Confirmed Worsening in Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts II and III Over the Treatment Period.

Tempo al peggioramento confermato del punteggio delle Parti II e III della Scala unificata di valutazione della malattia di Parkinson unificata della Società per i disturbi del movimento (MDS-UPDRS) durante il periodo di trattamento.

E.5.1.1

Timepoint(s) of evaluation of this end point

Up to Week 180

Fino alla Settimana 180

E.5.2

Secondary end point(s)

AEs: Day 1 up to Week 187; SAEs: Screening up to Week 187:
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Up to Week 180:
- Time to Confirmed Worsening in MDS-UPDRS Part II Score Over the Treatment Period

Baseline up to Week 96:
- Change From Baseline in MDS-UPDRS Parts II and III Combined Score

Up to Week 180:
- Time to Confirmed Worsening in Schwab and England Activities of Daily Living Scale (SE-ADL) Score Over the Treatment Period

Baseline up to Week 96:
- Change From Baseline in MDS-UPDRS Parts I, II, and III Combined Score

Eventi avversi (EA): dal Giorno 1 fino alla Settimana 187; eventi avversi seri (SAE): screening: fino alla Settimana 187:
- Numero di partecipanti con eventi avversi emergenti dal trattamento (TEAE) ed eventi avversi seri (SAE).

Fino alla Settimana 180:
- Tempo al peggioramento confermato del punteggio della Parte II della scala MDS-UPDRS durante il periodo di trattamento.

Basale fino alla Settimana 96:
- Variazione nel punteggio combinato delle Parti II e III della scala MDS-UPDRS dal basale.

Fino alla Settimana 180:
- Tempo al peggioramento confermato della Scala delle attività della vita quotidiana di Schwab e England (SEADL) durante il periodo di trattamento.

Basale fino alla Settimana 96:
- Variazione nel punteggio combinato delle Parti I, II e III della scala MDS-UPDRS
dal basale.

E.5.2.1

Timepoint(s) of evaluation of this end point

Timepoints mentioned in section E.5.2

Punti temporali menzionati nella sezione E.5.2

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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

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)

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

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

Information not present in EudraCT

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

Argentina

Brazil

Canada

Egypt

Israel

Tunisia

United States

France

Spain

Germany

Italy

Belgium

Norway

Portugal

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

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.1.1.1

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

125

F.4.2.2

In the whole clinical trial

400

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)

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

2022-11-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-10-12

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2023-05-25

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IMP with orphan designation in the indication
Orphan Designation Number:
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