Clinical Trials Register

Summary
EudraCT Number:	2017-003676-31
Sponsor's Protocol Code Number:	ROCK-ALS
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2018-04-25
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

France - ANSM

A.2

EudraCT number

2017-003676-31

A.3

Full title of the trial

Inhibition of Rho Kinase (ROCK) with Fasudil as disease-modifying treatment for ALS

A.3.1

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

Inhibition of Rho Kinase (ROCK) with Fasudil as disease-modifying treatment for ALS

A.4.1

Sponsor's protocol code number

ROCK-ALS

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	Georg-August-Universität Göttingen
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	Georg-August-Universität Göttingen
B.4.2	Country	Germany
B.4.1	Name of organisation providing support	CHU de Montpellier
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Münchner Studienzentrum
B.5.2	Functional name of contact point	Helen Bidner
B.5.3	Address:
B.5.3.1	Street Address	Ismaninger Strasse 22
B.5.3.2	Town/ city	München
B.5.3.3	Post code	81675
B.5.3.4	Country	Germany
B.5.4	Telephone number	+498941406312
B.5.5	Fax number	+498941406322
B.5.6	E-mail	helen.bidner@mri.tum.de

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	Eril®
D.2.1.1.2	Name of the Marketing Authorisation holder	Asahi Kasei Pharma Corporation
D.2.1.2	Country which granted the Marketing Authorisation	Japan
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	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	FASUDIL HYDROCHLORIDE
D.3.9.1	CAS number	105628-07-7
D.3.9.3	Other descriptive name	FASUDIL HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB21642
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	15
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	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

Amyotrophic lateral sclerosis

E.1.1.1

Medical condition in easily understood language

Amyotrophic lateral sclerosis is a devastating, progressive neurodegenerative disorder resulting in muscle weakness

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	10002026
E.1.2	Term	Amyotrophic lateral sclerosis
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

The primary objective of this phase IIa study (proof-of-concept study) is to evaluate the safety and tolerability until V23 after start of the intravenous application of the ROCK-inhibitor Fasudil (for 20 treatment days) in two different doses compared to placebo in patients with ALS.

E.2.2

Secondary objectives of the trial

A secondary aim is to assess the survival time and the change of ALSFRS-R, ALSAQ-5, ECAS and of vital capacity (VC) from baseline to V20, V22, and V23 days and MUNIX from baseline to V20, V22 and V23 after start of the intravenous application of the ROCK-inhibitor Fasudil. A further secondary aim is to determine safety and tolerability until V20.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

(1) Probable (clinically or laboratory) or definite ALS according to the revised version of the El Escorial World Federation of Neurology criteria
(2) Disease duration more than 6 months and less than 24 months (inclusive). Disease onset defined as date of first muscle weakness, excluding fasciculations and cramps
(3) Vital capacity more than 65% of normal (slow vital capacity; best of three measurements)
(4) Age: ≥ 18 years
(5) Patients have to be treated with Riluzole (2 x 50mg/d), must be stable for at least four weeks before randomization
(6) Patients who have started on Edaravone therapy shall continue Edaravone treatment. Edaravone treatment must not be discontinued for reasons of trial participation.
(7) Women of childbearing age must be non-lactating and surgically sterile or using a highly effective method of birth control and have a negative pregnancy test. Acceptable methods of birth control with a low failure rate i.e. less than 1% per year) when used consistently and correct are such as implants, injectables, combined oral contraceptives, hormonal intrauterine devices (IUDs), sexual abstinence or vasectomized partner
(8) Capable of thoroughly understanding all information given and giving full informed consent according to GCP
(9) Patients have to have a valid health insurance, when recruited in a center in France

E.4

Principal exclusion criteria

(1) Previous participation in another clinical study involving trial medication within the preceding 12 weeks or five terminal half times of the longest to be eliminated trial medications (whichever is longer) or previous participation in this trial
(2) Tracheostomy or continuous assisted ventilation of any type during the preceding three months before randomization or a significant pulmonary disorder not attributed to ALS, which may complicate the evaluation of respiratory function, intermittent non-invasive ventilation is permitted,
(3) Patients with a history of intracranial bleeding, known intracerebral aneurysms or Moyamoya disease, or positive family history for the above. If only family history positive, MR- or x-ray-based cranial imaging not older than 24 months must confirm absence of bleeding, aneurysms or Moyamoya.
(4) Gastrostomy
(5) Any medical condition known to have an association with motor neuron dysfunction or involving neuromuscular weakness or another neurodegenerative disease, e.g. PD or AD, which might confound or obscure the diagnosis of ALS
(6) Presence of any concomitant life-threatening disease or impairment likely to interfere with functional assessment
(7) Patients with known arterial hypotension (resting blood pressure <90/60 mmHg) or previous hypotensive episodes or requiring treatment for increasing of blood pressure, such as fludrocortiso-ne, midodrine, etilefrine, cafedrine or theodrenaline
(8) Patients with an uncontrollable or unstable arterial hypertensive disease (resting blood pressure >180 mmHg systolic and/or >120 mmHg diastolic under current antihypertensive medication)
(9) Known pulmonary hypertension and any medication prescribed for treatment of pulmonary hypertension
(10) Confirmed hepatic insufficiency or abnormal liver function (stable ASAT and/or ALAT greater than 3 times the upper limit of the normal range) and determined to be non-transient through repeat testing
(11) Renal insufficiency with a glomerular filtration rate (GFR) <60 ml/min/1,73m² (calculated by MDRD equation) and determined to be non-transient through repeat testing
(12) Major psychiatric disorder, significant cognitive impairment or clinically evident dementia precluding evaluation of symptoms
(13) Hypersensitivity to any component of the study drug
(14) Liable to be not cooperative or comply with the trial requirements (as assessed by the investigator), or unable to be reached in the case of emergency
(15) Pregnant or breast-feeding females or females with childbearing potential, if no adequate contraceptive measures are used
(16) Prisoners or subjects who are involuntary incarcerated
(17) Patients subject to legal protection measures

E.5 End points

E.5.1

Primary end point(s)

Primary endpoints are the proportion of patients without significant drug intolerances during the treatment period (tolerability) and the proportion of patients without treatment-related SAEs through to visit V23 (safety).

E.5.1.1

Timepoint(s) of evaluation of this end point

drug intolerances during the treatment period (tolerability): Treatment period ist from V1 till V20 (20 days)
proportion of patients without treatment-related SAEs through to visit V23 (safety): from V1 till V23 (180 days)

E.5.2

Secondary end point(s)

The survival time and the change of ALS Functional Rating Scale (ALSFRS-R), ALS Assessment Questionnaire (ALSAQ-5), Edinburgh Cognitive and Behavioral ALS Screen (ECAS), Motor Unit Number Index (MUNIX) and vital capacity (VC) from baseline to visits V20, V22, V23 after start of the intravenous application of the ROCK-inhibitor Fasudil (for 20 treatment days). Secondary safety endpoint is safety and tolerability until V20.

E.5.2.1

Timepoint(s) of evaluation of this end point

baseline, visits V20 (day 26) , V22 (day 90) and V23 (days 180)

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

Yes

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

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

France

Germany

Switzerland

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 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