Clinical Trials Register

Summary
EudraCT Number:	2021-003231-29
Sponsor's Protocol Code Number:	ATH434-201
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-01-13
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2021-003231-29

A.3

Full title of the trial

A Randomized, Double-Blind, Placebo-Controlled Study of ATH434 in Multiple System Atrophy

Studio randomizzato, in doppio cieco, controllato con placebo su ATH434 nell'atrofia multisistemica

A.3.1

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

A clinical study of ATH434 in patients with multiple system atrophy.

Uno studio clinico su ATH434 in pazienti con atrofia multisistemica

A.3.2

Name or abbreviated title of the trial where available

Study of ATH434 in Participants With Multiple System Atrophy

Studio su ATH343 in partecipanti con atrofia multisistemica

A.4.1

Sponsor's protocol code number

ATH434-201

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT05109091

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	Alterity Therapeutics Limited
B.1.3.4	Country	Australia
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	Alterity Therapeutics Limited
B.4.2	Country	Australia
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Alterity Therapeutics Limited
B.5.2	Functional name of contact point	Cynthia Wong
B.5.3	Address:
B.5.3.1	Street Address	39899 Balentine Drive, Suite 360
B.5.3.2	Town/ city	Newark, CA
B.5.3.3	Post code	94560
B.5.3.4	Country	United States
B.5.4	Telephone number	+16503002141
B.5.6	E-mail	cwong@alteritytherapeutics.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	Yes
D.2.5.1	Orphan drug designation number	EU/3/19/2228
D.3 Description of the IMP
D.3.1	Product name	NA
D.3.2	Product code	[ATH434]
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	2387898-69-1
D.3.9.2	Current sponsor code	ATH434
D.3.9.3	Other descriptive name	5,7-DICHLORO-2-((ETHYLAMINO)METHYL)-8-HYDROXY-3-METHYLQUINAZOLIN- 4(3H)-ONE MESILATE
D.3.9.4	EV Substance Code	SUB199187
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	50
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.IMP: 2
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	Yes
D.2.5.1	Orphan drug designation number	EU/3/19/2228
D.3 Description of the IMP
D.3.1	Product name	NA
D.3.2	Product code	[ATH434]
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	2387898-69-1
D.3.9.2	Current sponsor code	ATH434
D.3.9.3	Other descriptive name	5,7-DICHLORO-2-((ETHYLAMINO)METHYL)-8-HYDROXY-3-METHYLQUINAZOLIN- 4(3H)-ONE MESILATE
D.3.9.4	EV Substance Code	SUB199187
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
D.8 Placebo: 2
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

Multiple System Atrophy (MSA)

Atrofia multisistemica (MSA)

E.1.1.1

Medical condition in easily understood language

Atypical parkinsonism with impairment of the autonomic nervous system, gait instability and reduced muscle coordination

Parkinsonismo atipico con alterazione del sistema nervoso autonomo, instabilità della deambulazione e riduzione della coordinazione muscolare

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	10064060
E.1.2	Term	Multiple system atrophy
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

To assess the efficacy of ATH434 in subjects with MSA.

Valutare l’efficacia di ATH434 in soggetti affetti da MSA

E.2.2

Secondary objectives of the trial

- To assess the safety and tolerability of ATH434 in subjects with MSA
- To evaluate the pharmacokinetics (PK) of ATH434 and potential metabolites in subjects with MSA

- Valutare la sicurezza e la tollerabilità di ATH434 in soggetti affetti da MSA
- Valutare la farmacocinetica (PK) di ATH434 e dei potenziali metaboliti in soggetti affetti da MSA

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subject is 30 to 78 years old at the time of Screening.
2. Subject has provided written informed consent.
3. Subject has clinical features of parkinsonism.
4. Subject has evidence of autonomic dysfunction.
5. Subject has additional features (ataxia or pyramidal sign[s]) of MSA.
6. Subject is able to ambulate without assistance.
7. Stable medical treatment for MSA symptoms.
8. Female and male subjects must meet contraception requirements of study.

1. il soggetto ha un’età compresa tra 30 e 78 anni inclusi, al momento dello screening;
2. il soggetto ha fornito il consenso informato scritto;
3. il soggetto presenta caratteristiche cliniche di parkinsonismo;
4. il soggetto presenta caratteristiche di disfunzione autonomica:
5. il soggetto presenta almeno una caratteristica aggiuntiva di MSA (atassia o presenza di segni piramidali) :
6. il soggetto è in grado di deambulare senza assistenzai;
7. sta ricevendo una terapia stabile per i sintomi da MSA
8. I soggetti femminili e maschili devono rispecchiare i requisiti dello studio per la contraccezione

E.4

Principal exclusion criteria

1. Subject has long duration of motor symptoms.
2. Subject has evidence of swallowing impairment.
3. Subject has frequent falls.
4. Subject has evidence of cognitive impairment/Dementia with Lewy bodies
5. Subject has evidence of ischemic damage or structural brain abnormality on Screening MRI.
6. Subject has any significant neurological disorder other than MSA.
7. Subject has a contraindication or inability to tolerate brain MRI or lumbar puncture.
8. Subject is receiving prohibited concomitant medication.
9. Subject has an unstable medical or psychiatric illness.
10. Subject resides at a skilled nursing facility.
11. Subject has participated in an investigational study of a potential disease-modifying therapy within 6 months.
12. Subject has participated in an investigational study of a symptomatic therapy within 30 days or 5 half-lives, whichever is longer.

1. il soggetto ha manifestato sintomi motori da molto tempo
2. il soggetto presenta compromissione della deglutizione;
3. il soggetto cade di frequente;
4. il soggetto presenta evidenza di compromissione cognitiva/demenza con corpi di Lewy;
5. Il soggetto presenta danno ischemico o anormalità cerebrale strutturale alla MRI di screening
6. il soggetto presenta evidenza di qualsiasi disturbo neurologico significativo diverso da MSA:
7. il soggetto presenta una controindicazione o incapacità di tollerare la RMI cerebrale o la puntura lombare;
8. il soggetto sta ricevendo farmaci concomitanti proibiti;
9. il soggetto ha una malattia medica o psichiatrica instabile
10. il soggetto risiede in una struttura infermieristica specializzata
11. il soggetto ha partecipato a uno studio sperimentale di una terapia putativa modificante la malattia entro 6 mesi
12. il soggetto ha partecipato a un studio sperimentale di una terapia sintomatica entro 30 giorni (o 5 emivite del farmaco), a seconda di quale sia il periodo più lungo.

E.5 End points

E.5.1

Primary end point(s)

change in iron content as measured by brain MRI

modifica nel contenuto/accumulo di ferro misurata mediante RMI cerebrale.

E.5.1.1

Timepoint(s) of evaluation of this end point

MRI will be performed at
Screening, Week 26 and Week 52 visits.

La RMI sarà svolta allo screening, alla visita della settimana 26 e alla visita della settimana 52.

E.5.2

Secondary end point(s)

- UMSARS Part I
- Motor Examination
- SF-36
- Neurofilament light chain
- Aggregating a-synuclein

• Scala unificata di valutazione dell’atrofia multisistemica (Unified Multiple System Atrophy Rating Scale, UMSARS) Parte I
• Valutazione motoria;
• SF-36.
• catena leggera dei neurofilamenti
• a-sinucleina aggregante

E.5.2.1

Timepoint(s) of evaluation of this end point

Changes from Baseline (Day 1) to Week 52 (in-clinic visits Day 1, Week 13, 26, 39 and 52).; Cambiamenti dal Basale (Giorno 1) alla settimana 52 (visite in ospedale al giorno 1, settimana 13, 26, 39 e 52)

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

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

Australia

France

Italy

New Zealand

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

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

F.4.2.2

In the whole clinical trial

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

Nessuno

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

2022-04-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-07-26

P. End of Trial
P.	End of Trial Status	Ongoing

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