Amyotrophic Lateral Sclerosis MedDRA version: 21.1 Level: PT Classification code 10002026 Term: Amyotrophic lateral sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Sponsors
Ferrer Internacional, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
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. 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. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. • 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. A vasectomised partner is a highly effective contraception method provided that the partner is the sole male sexual partner of the WOCBP and the absence of sperm has been confirmed. If not, an additional highly effective method of contraception should be used. 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 inhi
Exclusion criteria
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. 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; 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 outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effect of treatment with 100 mg of FAB122 on disease progression in patients with ALS;Secondary Objective: 1.To evaluate the effect of treatment with FAB122 on survival 2.To evaluate the safety and tolerability of FAB122 3.To evaluate the effect of treatment with FAB122 on quality of life (QoL) 4.To evaluate the effect of treatment with FAB122 on cognitive functioning 5.To evaluate the pharmacokinetics (PK) of FAB122 ;Primary end point(s): Change from baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale – Revised (ALSFRS-R) score after 48 weeks;Timepoint(s) of evaluation of this end point: After 48 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 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; 2. The slope of the decrease in ALSFRS-R score over time at 24, 48 and 72 weeks; 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, 48 and 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, 48, and 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, 48, and 72 weeks 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, 48, and 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, 48, and 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, 48, and 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 D | — |
Countries
Belgium, France, Germany, Ireland, Italy, Netherlands, Poland, Portugal, Russian Federation, Spain, Sweden, United Kingdom
Contacts
Public ContactProject Manager
Julius Clinical
Outcome results
None listed