Clinical Trials Register

Summary
EudraCT Number:	2015-000460-34
Sponsor's Protocol Code Number:	ALCAT
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-11-11
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

Austria - BASG

A.2

EudraCT number

2015-000460-34

A.3

Full title of the trial

Effects of Acetyl-DL-Leucine on cerebellar ataxia - a multinational, multicenter, randomized, double-blind, placebo-controlled, 2-way crossover phase III trial (ALCAT)

Wirksamkeit von Acetyl-DL-Leucin bei Patienten mit cerebellärer Ataxie –eine multinationale, multizentrische, randomisierte, doppelblinde, placebo-kontrollierte, Phase III Studie im crossover Design

A.3.1

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

Effects of Acetyl-DL-Leucine on cerebellar ataxia

Wirksamkeit von Acetyl-DL-Leucin bei Patienten mit Kleinhirnerkrankungen

A.3.2

Name or abbreviated title of the trial where available

ALCAT

A.4.1

Sponsor's protocol code number

ALCAT

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	Hospital of the University of Munich
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Bundesministerium fuer Forschung und Bildung (BMBF)
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Hospital of the University of Munich
B.5.2	Functional name of contact point	DSGZ Studienzentrale
B.5.3	Address:
B.5.3.1	Street Address	Marchioninistrasse 15
B.5.3.2	Town/ city	Munich
B.5.3.3	Post code	81377
B.5.3.4	Country	Germany
B.5.4	Telephone number	0049089440076987
B.5.5	Fax number	0049089440078795

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	Yes
D.2.1.1.1	Trade name	Tanganil
D.2.1.1.2	Name of the Marketing Authorisation holder	Pierre Fabre Medicament
D.2.1.2	Country which granted the Marketing Authorisation	France
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.3.4	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.3.8	INN - Proposed INN	ACETYLLEUCINE
D.3.9.3	Other descriptive name	Tanganil
D.3.9.4	EV Substance Code	SUB05231MIG
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	500
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	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	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

Cerebellar ataxia is a form of ataxia originating in the cerebellum and is most often caused by neurodegenerative disorders of the cerebellum, either hereditary or sporadic. The leading clinical symptoms of cerebellar ataxia are disturbances of stance/gait (> 85%) with recurrent falls, limb ataxia with severe functional impairment of arm and hand movements, dysarthrophonia with impaired oral communication abilities and ocular motor disturbances with impaired vision.

E.1.1.1

Medical condition in easily understood language

Cerbellar ataxia is a neurodegenerative neurological disorder characterized by disturbances of gait, imbalance, speech and motor skills

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

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

The primary aim of the ALCAT trial is to determine the effect of Acetyl-DL-Leucine compared to placebo intervention on improving motor function measured by the total score of the Scale for the Assessment and Rating of Ataxia (SARA).

E.2.2

Secondary objectives of the trial

To demonstrate that Acetyl-DL-Leucine is efficacious in
1. improving motor function measured by the Spinocerebellar Ataxia Functional Index (SCAFI) and SARA subscore items
2. improving quality of life (EQ-5D-5L) as well as depression (Beck Depression Inventory, BDI-II) and fatigue (Fatigue Severity Score, FSS)
3. to check for the occurrence of adverse effects of the trial drug.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Subjects will only be included in the study if they meet all of the following criteria:
1) Clinically confirmed cerebellar ataxia (CA) with a total SARA-Score ≥ 3 (range 0-40) of hereditary or non-hereditary degenerative type
2) Patient did not receive any of the following prohibited medication within 4 weeks prior to randomization: aminopyridines, Acetyl-DL-Leucine, Riluzole, Gabapentin, Varenicline, Chlorzoxazone
3) The ability to follow study instructions and likely to attend and complete all required visits
4) Written informed consent of the subject prior to any study specific intervention
5) Age ≥ 18 years

E.4

Principal exclusion criteria

Subjects will not be included in the study if any of the following criteria applies:
1) Subject is not able to give consent
2) Onset of ataxia in association with stroke, encephalitis, sepsis, hyperthermia or heat stroke
3) Toxic causes for ataxia of cerebellar type
4) Rapid progression of ataxia (development of severe ataxia in less than 12 weeks)
5) Subject suffers from any of the following:
o chronic diarrhea
o unexplained visual loss
o malignancies
o insulin-dependent diabetes mellitus
6) Ataxia due to multiple sclerosis, ischemia, hemorrhage or tumor of the posterior fossa as confirmed by imaging
7) Ataxia due to clinical likely multisystem atrophy type C (MSA-C)
8) Diagnosis of clinical likely Friedreich ataxia
9) Known history of hypersensitivity to the investigational drug or derivates
10) Liver failure defined as AST/ALT > 300 U/l
11) Simultaneous participation in another clinical trial or participation in any clinical trial involving administration of an investigational medical product within 30 days prior to the beginning of the clinical trial
12) Subjects with a physical or psychiatric condition which at the investigator’s discretion may put the subject at risk, may confound the trial results, or may interfere with the subject’s participation in this clinical trial
13) Known or persistent abuse of medication, drugs or alcohol
14) Females of childbearing potential, who are not using and not willing to use medically reliable methods of contraception for the entire study duration as listed in the patient informed consent form
15) Current or planned pregnancy or nursing women
16) Patient has received any of the following prohibited medication within 4 weeks prior to randomization
o Aminopyridines (including substained-release form)
o Acetyl-DL-Leucine
o Riluzole
o Gabapentin
o Varenicline
o Chlorzoxazone

E.5 End points

E.5.1

Primary end point(s)

Primary efficacy endpoint:
The primary efficacy endpoint is defined as the absolute changes in SARA total score from period-level baseline to week 2 after start of treatment start and to the end of the 6-weeks treatment period, i.e. the difference between post-treatment values and the corresponding period-level baseline values:

Delta (SARAtotal) = SARAtotal (post-treatment) – SARAtotal (period baseline)

E.5.1.1

Timepoint(s) of evaluation of this end point

after 2 and 6 weeks of treatment with IMP (for each treatment period)

E.5.2

Secondary end point(s)

Key secondary endpoint(s):
SCAFI and subscores of SARA, QoL (EQ-5D-5L), depression (BDI-II), fatigue (FSS)

Assessment of safety:
Documentation and reporting of side effects (AEs, SAEs, SUSARs)

E.5.2.1

Timepoint(s) of evaluation of this end point

6 weeks of treatment with IMP (for each treatment period) as well as in follow-up 4 weeks after taking the last IMP.
Absolute changes at the end of the 6-week treatment period compared to the period-level baseline defined as score at visit 2 (treatment period 1) and at visit 5 (treatment period 2) as well as 4 weeks after taking the last IMP (follow-up).

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

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)

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

E.8.1.6

Cross over

Yes

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

Yes

E.8.4

The trial involves multiple sites in the 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

E.8.6.2

Trial being conducted completely outside of the EEA

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

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

108

F.4.2.2

In the whole clinical trial

108

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)

All patients are already known in the clinicals and study centers. Thus, the follow-up and medical care after the end of the clinical trial is possible for the patients, because they are regularly seen in clinical follow-up examinations. The medical file will contain details about the participation in the clinical trial with all collected clinical findings. If a patient improved under the drug tested in the trial, further treatment with this IMP could be offered by the study centers.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	Deutsche Heredo-Ataxie Gesellschaft Bundesverband eV
G.4.3.4	Network Country	Germany

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2015-12-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-01-05

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-07-07

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