To assess the effect of treatment with 100 mg of FAB122 (edaravone) on disease progression in patients with ALS.
ID
Source
Brief title
Condition
- Neuromuscular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Change from baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale -
Revised (ALSFRS-R) score after 48 weeks.
Secondary outcome
Key secondary endpoints;
1. Combined assessment of function and survival (CAFS) at 48 and 72 weeks;
2. Survival time, i.e. time to death, tracheostomy or initiation of
non-invasive ventilation for more than 20 hours a day for more than 10
consecutive days, over 72 weeks
Efficacy;
1. Change from baseline in ALSFRS-R score after 24 and 72 weeks of treatment;
2. The slope of the decrease in ALSFRS-R score over time at 24, 48and 72 weeks
of treatment;
3. Change from baseline in ALSFRS-R score on Bulbar function (question 1-3 of
the ALSFRS-R) after 24, 48 and 72 weeks;
4. Change from baseline in ALSFRS-R score on Fine motor function (question 4-6
of the ALSFRS-R) after 24, 48and 72 weeks;
5. Change from baseline in ALSFRS-R score on Gross motor function (question 7-9
of the ALSFRS-R) after 24, 48 and 72 weeks;
6. Change from baseline in ALSFRS-R score on Respiratory function (question
10-12 of the ALSFRS-R) after 24, 48and 72 weeks;
7. Time to a 3, 6, 9 and 12 points change or death from baseline in ALSFRS-R
score, over 72 weeks ;
8. Proportion of subjects with change from baseline in ALSFRS-R score at 24,
48and 72 weeks of treatment in categories: categories will include change >=0,
change between <0 and >=-1, change between <-1 and >=-2 etc.;
9. Time to change in clinical staging or death (King*s staging system and
MiToS) over 72 weeks;
10. Overall survival: Proportion of subjects alive (survival rate) after 24,
48and 72 weeks;
11. Proportion of subjects alive and no tracheostomy, or no initiation of
non-invasive ventilation for more than 20 hours a day for more
than 10 consecutive days after 24, 48and 72 weeks;
12. Change from baseline in slow vital capacity (SVC, liters) at 24, 48 and 72
weeks;
13. Change from baseline in the overall mega score for the hand-held
dynamometer (HHD) at 24, 48and 72 weeks.
Qol;
1. Change from baseline in the total score on the ALS Assessment
Questionnaire-40-Item (ALSAQ-40) Form at 24, 48 and 72 weeks
2. Change from baseline in EuroQoL - 5 Dimensions-5 Levels (EQ-5D-5L)
questionnaire score and health related QoL at 24, 48 and 72 weeks .
3. Change from baseline in Visual Analogue Scale (VAS) score at 24, 48 and 72
weeks of treatment.
Cognition;
1. Proportion of subjects with a change of >=8, >=4, and >=9 for ALS Specific, ALS
Non-Specific, and ECAS (Edinburgh Cognitive and
behavioural ALS Screen) total score;
2. Change from baseline for ALS Specific, ALS Non-Specific, and ECAS total
score at 24, 48 and 72 weeks;
3. Time to a mean change of >=8, >=4, and >=9 for ALS Specific, ALS Non-Specific,
and ECAS total score.
Pharmacokinetics;
(Population) PK parameters of FAB122 and riluzole
Background summary
ALS is a very serious and fatal condition characterized by progressive
degeneration of the upper and lower motor neurons.
Clinically ALS is characterized by muscle weakness and functional decline.
There are limited pharmacological options in the
treatment of ALS, and they focus mainly on symptomatic treatment. The only
existing authorized medicine for treating ALS in the
European Union is Riluzole.
Results from previous phase II and Ill clinical studies in ALS patients
administered IV FAB122 (edaravone) demonstrated the
potential of edaravone for the treatment of ALS. The data from these studies
led to the approval of IV-administered edaravone for
the inhibition of ALS disease progression in Japan, the US, Canada and
Switzerland. However, chronic IV administration has
significant drawbacks, including the risk of both local and systemic side
effects. The involvement of medical staff at home or the
daily presence in the hospital for administration also complicates compliance
with the medicine. In addition, during the necessary
treatment holidays of 14 days per month, no exposure to the drug is obtained.
These drawbacks can be overcome by administration of the oral FAB 122
formulation as proposed in this study, and given the
exposure-based efficacy of edaravone, a longer-term exposure profile may
further enhance edaravone's efficacy in ALS. This can
be achieved by once daily dosing of orally administered FAB122 without a drug
break. This study is expected to benefit the ALS
patient population, in general, as well as the patients participating in this
study.
Study objective
To assess the effect of treatment with 100 mg of FAB122 (edaravone) on disease
progression in patients with ALS.
Study design
Multicenter, multinational, double-blind, randomized (2:1 ), placebo-controlled
Phase Ill study to investigate the efficacy and safety of
100 mg FAB122 once daily as oral formulation in ALS patients.
Double-blind treatment is planned to continue for all subjects until the last
randomized subject has reached at least 48 weeks of
treatment AND at least one third of the subjects has reached 72 weeks of
treatment. The maximum treatment duration for a subject
in this study is 72 weeks
Subjects will visit the clinic at Screening, Baseline, Week 4, Week 12, and
every 12 weeks thereafter. Monthly telephone visits are
performed in between the visits to the clinic until Week 48.
After a subject completed the study (max at 72 weeks), he/she will be offered
the possibility to roll over in an open label extension
trial in which all subjects will be offered to receive FAB122.
Intervention
Patients will take study medication daily for the entire duration of the study,
from day 1 up to a maximum of 72 weeks. It concerns a
fasting daily dose of 100 mg of FAB 122 granules for oral solution in a few
sachets, which must be dissolved in 100 ml of water
before administration, or matching placebo in a ratio of 2: 1, respectively.
Study burden and risks
Advantages
It is possible that the study drug will slow the development of ALS, but it is
also possible that the development of ALS will continue despite use of this
drug. It may be that participating in this study will not provide any benefit
to your health. But with your participation, you will help researchers gain a
better understanding of how to treat ALS.
Disadvantages
Disadvantages of participation in the study may be:
- possible side effects of the study drug.
- possible adverse effects/discomforts of the tests and procedures applied in
the study.
- taking medication according to study procedures.
Participation in the study also means:
- That you have to invest time in participation in the study
- That you have to attend (additional) clinic visits, undergo testing, and be
available for telephone calls.
Diagonal 549
Barcelona 08029
ES
Diagonal 549
Barcelona 08029
ES
Listed location countries
Age
Inclusion criteria
1. Age 18 - 80 years (both inclusive), male or female;
2. Diagnosis of definite, probable, probable laboratory supported or possible
ALS as based on the El Escorial and the revised Airlie House diagnostic
criteria for ALS;
3. Onset of first symptoms* no longer than 24 months prior to randomization;
*Date of onset is the date the patient reported one or more of the following
symptoms: Muscle weakness in limbs; speech/swallowing difficulties; respiratory
symptoms: dyspnea was noticed
4. Slow Vital Capacity (SVC) equal to or more than 70% of the predicted normal
value for gender, height and age at screening visit;
5. Change in ALSFRS-R score between 0.35 points and 1.5 points per month (both
inclusive) in the period from onset of first symptoms to the Screening visit;
6. Patients on riluzole should be on stable doses >=30 days prior to the
baseline visit and this dose should be maintained during the entire trial.
7. A female subject should not be able to become pregnant and needs to meet at
least one of the following criteria:
• female subject who is not of reproductive potential is eligible without
requiring the use of contraception. A woman is considered not having
childbearing potential when becoming post-menopausal unless permanently
sterile. Permanent sterilisation methods include hysterectomy, bilateral
salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as
no menses for 12 months without an alternative medical cause. female who is of
reproductive potential and has a negative pregnancy test at screening and at
baseline and is non-lactating. A female subject who is of reproductive
potential agrees to use (or have their partner use) or practicing adequate
birth control methods starting from the time of consent through 30 days after
the last dose of study therapy. Longer periods of birth control may be required
per local requirements. Acceptable methods of birth control include combined
(estrogen and progestogen containing) hormonal contraception associated with
inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only
hormonal contraception associated with inhibition of ovulation (oral,
injectable, implantable), intrauterine device in place for >=3months,
intrauterine hormone-releasing system, bilateral tubal occlusion or
vasectomised partner.;
8. A male patient must: • agree he will not donate sperm during the study and
until 104 days after the last dose, AND • use a condom during sexual
intercourse with pregnant or non-pregnant women of childbearing potential
(WOCBP) partner even if he is vasectomized • in addition WOCBP partner of the
male patient must use the following acceptable methods of birth control during
the study and until 104 days after the last dose: combined (estrogen and
progestogen containing) hormonal contraception associated with inhibition of
ovulation (oral, intravaginal, transdermal), progestogen-only hormonal
contraception associated with inhibition of ovulation (oral, injectable,
implantable), intrauterine device in place for >=3 months, intrauterine
hormone-releasing system, bilateral tubal occlusion or vasectomised partner;
9. Capable of providing informed consent and complying with trial procedures.
Exclusion criteria
1. Diagnosis of Primary Lateral Sclerosis;
2. Diagnosis of Frontotemporal Dementia;
3. Diagnosis of other neurodegenerative diseases (e.g. Parkinson disease,
Alzheimer disease);
4. Diagnosis of polyneuropathy;
5. Other causes of neuromuscular weakness;
6. Have a significant pulmonary disorder not attributed to ALS and/or require
treatment interfering with the evaluation of ALS on respiratory function;
7. Use of intravenous (IV) edaravone within 6 months of the screening visit;
8. Use of mechanical ventilation (invasive or non-invasive) at Screening;
9. Renal impairment as indicated by a creatinine clearance of less than 50
mL/min;
10. Subject has a history of clinically significant hepatic disease, hepatitis
or biliary tract disease, ALT/AST levels >= 3xULN, bilirubin levels >=2xULN or
subject has a positive screening test for HIV, hepatitis B or C;
11. Presence of any of the following clinical conditions:
a. Unstable cardiac, pulmonary, endocrine, hematologic or active infectious
disease
b. Severe active psychiatric illness e.g psychosis, untreated major depression
within 90 days of the screening visit
c. Significant cognitive impairment, clinical dementia or psychiatric illness
d. Cancer that is currently under active treatment or is likely to require
treatment during the trial that may alter the subject*s function and interfere
with assessment of ALS disease progression.
12. Any comorbidity that may interfere with the functions as scored with the
ALSFRS-R;
13. History of known sensitivity or intolerability to edaravone, to any related
compound, or to any of the excipients;
14. Exposure to any investigational drug within 30 days of the screening visit
or 5 half-lives, whichever is longer;
15. Current substance or alcohol dependence;
16. For patients undergoing optional CSF sampling: any condition that according
to the investigator criteria is contraindicated for the procedure (e.g.
space-occupying lesion with mass effect, increase of intracranial pressure due
to increased CSF pressure; posterior fossa mass; Arnold-Chiari malformation;
anticoagulant medication; coagulopathy; uncorrected bleeding diathesis;
congenital spine abnormality; and skin infection at puncture site.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-003376-40-NL |
| CCMO | NL79225.041.21 |