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 of treatment.
Secondary outcome
Key secondary endpoints;
1. Combined assessment of function and survival (CAFS) at 48 and 72 weeks of
treatment;
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 of treatment.
Efficacy;
1. Change from baseline in ALSFRS-R score after 12, 24, 60, 72 weeks of
treatment;
2. The slope of the decrease in ALSFRS-R score over time at 24, 48, 60 and 72
weeks of treatment;
3. Absolute ALSFRS-R score per assessment time point;
4. Change from baseline in ALSFRS-R score on Bulbar function (question 1-3 of
the ALSFRS-R) after 12, 24, 60 and 72 weeks of treatment;
5. Change from baseline in ALSFRS-R score on Fine motor function (question 4-6
of the ALSFRS-R) after 12, 24, 60 and 72 weeks of treatment;
6. Change from baseline in ALSFRS-R score on Gross motor function (question 7-9
of the ALSFRS-R) after 12, 24, 60 and 72 weeks of treatment;
7. Change from baseline in ALSFRS-R score on Respiratory function (question
10-12 of the ALSFRS-R) after 12, 24, 60 and 72 weeks of treatment;
8. Time to a 3, 6, 9 and 12 points change from baseline in ALSFRS-R score;
9. Proportion of subjects with change from baseline in ALSFRS-R score at 24,
48, 60 and 72 weeks of treatment in categories: categories will include change
*0, change between <0 and *-1, change between <-1 and *-2 etc.;
10. Staging of disease progression (King*s staging system and MiToS);
11. Overall survival: Proportion of subjects alive (survival rate) after 24,
48, 60 and 72 weeks of treatment;
12. 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, 48, 60 and 72 weeks of treatment;
13. Absolute value and change from baseline in slow vital capacity (SVC,
liters) at 24, 48, 60 and 72 weeks of treatment;
14. Absolute value and change from baseline in the overall mega score for the
hand-held dynamometer (HHD) at 24, 48, 60 and 72 weeks of treatment.
QoL;
1. Absolute values and change from baseline in the total score on the ALS
Assessment Questionnaire-40-Item (ALSAQ-40) Form at 24, 48 and 72 weeks of
treatment;
2. Absolute values and change from baseline in EuroQoL * 5 Dimensions-5 Levels
(EQ-5D-5L) questionnaire score and health related QoL at 24, 48, 60 and 72
weeks of treatment.
3. Visual Analogue Scale (VAS) score at 24, 48, 60 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. 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 III 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 FAB122
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 III 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 FAB122 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
Your current condition of ALS will be assessed carefully. The study drug may
slow down ALS disease progression, but this is not certain. It may be that
participation in this study does not provide you any benefit for your health.
However, you will contribute to increase the knowledge about the treatment of
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 *3 months,
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: hormonal contraception (oral, implanted, injected or other
hormonal (e.g., patch or contraceptive ring) contraception), intrauterine
device in place for *3 months, barrier method in conjunction with spermicide OR
use of appropriate
double barrier contraception as per local regulations or guidelines;
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. Depend on mechanical ventilation (invasive or non-invasive) or require
tracheostomy at Screening;
9. Renal impairment as indicated by a creatinine clearance of less than 50
mL/min as calculated by the Cockcroft Gault equation;
10. Subject has a history of clinically significant hepatic disease, hepatitis
or biliary tract disease, 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. Unstable
psychiatric illness defined as 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;
15. Current substance or alcohol dependence.
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 | NL74715.041.21 |