Study of safety and of the mechanism of BLZ945 in amyotrophic lateral sclerosis (ALS) patients.
- Conditions
- Amyotrophic lateral sclerosis (ALS)MedDRA version: 21.1Level: PTClassification code 10002026Term: Amyotrophic lateral sclerosisSystem Organ Class: 10029205 - Nervous system disordersTherapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2019-000826-22-SE
- Lead Sponsor
- ovartis Pharma AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 56
1. Cohorts 1-5: Able to communicate well with the investigator, to
understand and comply with the study visits and procedures of the
study.
2. Cohorts 1-5: Written informed consent must be obtained before any assessment is performed.
3. Cohorts 1-5: Male and female participants who are = 18 years at
screening, and who are diagnosed with familial or sporadic ALS
according to the World Federation of Neurology Revised El Escorial
criteria of either bulbar or limb onset.
4. Cohorts 1-4: Able to swallow medication capsules, in the opinion of
the investigator.
5. Cohorts 1-5: Disease duration from symptoms onset no longer than 48 months at the screening visit.
6. Cohorts 1-4 and Cohort 5 (PET sub-study): Having a SVC (slow vital
capacity) equal to or more than 60% predicted normal value per local
standards for gender, height, and age at the screening visit.
7a. Cohorts 1-5: Females of childbearing potential must have a negative pregnancy test at screening and/or baseline.
8. Cohorts 1-4 and Cohort 5 (PET sub-study): High-affinity binders
(HAB) to TSPO as evaluated by genotyping for the rs6971 polymorphism
in the TSPO gene at the screening visit.
9. Cohorts 1-4 and Cohort 5 (PET sub-study): Baseline PET scan of
sufficient image quality, as determined locally by the PET experts, to
enable the measurement of [11C]-PBR28 volume of distribution (Vt) in the relevant CNS regions.
10b. Cohort 1-5: Treatment with currently approved therapies is allowed, but participants need to be on a stable dose and regimen for at least 30 days prior to baseline. In case of riluzole, participants need to be on stable dose and regimen for at least 90 days prior to baseline. In case for edaravone, the participant can be included if the initial BLZ945 dosing days can be scheduled off period of the edavarone treatment regimen.
11. Cohorts 1-4 and Cohort 5 (PET sub-study): An Upper Motor Neuron Burden (UMNB) scale =25 at the screening visit
12. Cohorts 1-4 and Cohort 5 (PET sub-study): BMI between 18-35
kg/m2 at the screening visit.
13. Cohort 5 extended treatment period: Written informed consent for the extended treatment must be obtained before any assessment in the extended treatment period is performed.
14. Cohort 5 extended treatment period: Having completed the 12-week treatment period. and the 4-week follow-up.
15. Cohort 5 extended treatment period: Females of childbearing
potential must have a negative pregnancy test at Week 16 and agree to continue the contraception methods used in the treatment period.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 32
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 14
1a. Cohorts 1-5: A history of clinically significant ECG abnormalities
2. Cohorts 1-5: Active hematologic, hepatic, respiratory disorders that
are clinically significant and may jeopardize the patient's safety if
participating in the study or limit his/her participation in the study,
including ability to tolerate the imaging studies.
3. Cohorts 1-5: Active dementia, neurologic diseases other than ALS, or psychiatric illness that in the opinion of the investigator would limit their participation in the current study.
4. Cohorts 1-5: Use of other investigational drugs within 5 half-lives of
screening, or until the expected PD effect has returned to baseline ,
whichever is longer; or longer if required by local regulations.
5. Cohorts 1-5: History of hypersensitivity to any of the study treatments or excipients or to drugs of similar chemical classes.
6. Cohorts 1-5: Presence of human immunodeficiency virus (HIV)
infection based on screening lab results .
7. Cohorts 1-5: Evidence of active or latent tuberculosis as assessed by Quantiferon or similar testing as per local practice at screening.
8. Cohorts 1-5: Positive serology for hepatitis B surface antigen, or
hepatitis C antibodies confirmed by an appropriate licensed test at
screening.
9a. Cohorts 1-5: Signs or symptoms, in the judgement of the
investigator, of a clinically significant systemic viral, bacterial or fungal
infection within 30 days prior to the screening visit. COVID-19
specifically: testing as per local practice for COVID-19 will be completed within 3 days prior to first dosing. Positive COVID-19 test results would exclude participants from being enrolled into this study.
10a. Cohorts 1-5: Cardiac disorders, such as recent cardiac history
(within 6 months of screening) of acute coronary syndrome, acute heart failure, or significant ventricular arrhythmia at the screening visit or participants with a history of severe pulmonary hypertension, or cardiac failure class 3 or 4 of the NYHA classification, or history of reduced LVEF (<45%), or individuals with implanted cardiac pacemaker, or defibrillator.
11. Cohorts 1-5: Significant haematological laboratory abnormalities.
12. Cohorts 1-5: Clinical evidence of liver disease or liver injury or any of the following hepatic conditions at the screening visit
13. Cohorts 1-5: Women of child-bearing potential, unless they are using highly effective methods of contraception during dosing and for 14 days after last dose of BLZ945.
14. Cohorts 1-5: Pregnant or nursing female subjects
15. Cohorts 1-5: Sexually active males unless they use condom during
intercourse during treatment, for 14 days after stopping BLZ945 and
should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via semen.
16. Intentionally left blank: removed in amendment 02
17. Cohorts 1-4 and Cohort 5 (PET sub-study): Any contraindications to MRI
18. Cohorts 1-5: Taking medications prohibited by the protocol
19a. Cohorts 1-4 and Cohort 5 (PET sub-study): Any contraindications to the arterial line sampling
20. Cohorts 1-5: History or presence of impaired renal function as
indicated by clinically significantly abnormal creatinine or BUN and/or
urea values, or abnormal urinary constituents at the screening visit.
21. Cohorts 1-5: Active suicidal ideation
22a. Cohorts 1-5: History of drug abuse or harmful alcohol use within the 12 months prior to dosing within the judgement of the investigat
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method