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

Phase 2

• Conditions: Amyotrophic lateral sclerosis (ALS); G12.2; Motor neuron disease

• Registration Number: DRKS00013948
• Lead Sponsor: Georg-August-Universität Göttingen, Stiftung Öffentlichen Rechts, Universitätsmedizin Göttingen

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-01-10
• Study Completion: 2022-11-09
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Complete
• Sex: All
• Target Recruitment: 120

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

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

Study & Design

• Study Type: interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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 though to day 180 (safety)

Secondary Outcome Measures

Name	Time	Method
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 days 26, 90, 180 after start of the intravenous application of the ROCK-inhibitor Fasudil (for 20 treatment days). Secondary safety endpoint is safety and tolerability until day 26.