Study of safety and of the mechanism of BLZ945 in amyotrophic lateral sclerosis (ALS) patients.

Phase 1

• Conditions: Amyotrophic lateral sclerosis (ALS); MedDRA version: 21.1Level: PTClassification code 10002026Term: Amyotrophic lateral sclerosisSystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2019-000826-22-FI
• Lead Sponsor: ovartis Pharma AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-09-18
• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 56

Inclusion Criteria

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 riluzole and/or edaravone are 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 in the 20 days 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

Exclusion Criteria

1a. Cohorts1-5:A history of clinically significant ECG abnormalities
2.Cohorts1-5:Active hematologic,hepatic,respiratory disorders that are clinically significant & may jeopardize the patients safety if participating in the study or limit his/her participation in study, including ability to tolerate the imaging studies.
3.Cohorts1-5:Active dementia,neurologic diseases other than ALS, or psychiatric illness that in opinion of investigator would limit their participation in current study.
4.Cohorts1-5: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.Cohorts1-5:History of hypersensitivity to any of study treatments or excipients or to drugs of similar chemical classes.
6.Cohorts1-5:Presence of human immunodeficiency virus(HIV) infection based on screening lab results
7.Cohorts1-5: Evidence of active or latent tuberculosis as assessed by Quantiferon or similar testing as per local practice at screening.
8.Cohorts1-5: Positive serology for hepatitis B surface antigen,or hepatitis C antibodies confirmed by an appropriate licensed test at screening.
9a.Cohorts1-5:Signs or symptoms, in the judgement of investigator, of a clinically significant systemic viral, bacterial or fungal infection within 30 days prior to screening visit. COVID-19 specifically:testing as per local practice for COVID-19 will be completed within 3days prior to first dosing.Positive COVID-19 test results would exclude participants from being enrolled into this study.
10a.Cohorts1-5:Cardiac disorders,such as recent cardiac history
(within 6months 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.Cohorts1-5:Significant haematological laboratory abnormalities.
12.Cohorts1-5:Clinical evidence of liver disease or liver injury or any of following hepatic conditions at screening visit
13.Cohorts1-5:Women of child-bearing potential,defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 14 days after last dose of BLZ945.
14.Cohorts1-5:Pregnant or nursing female subjects
15.Cohorts1-5:Sexually active males unless they use a condom during intercourse while taking the drug 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.Cohorts1-4 and Cohort 5 (PET sub-study): Any contraindications to MRI
18.Cohorts1-5: Taking medications prohibited by the protocol
19a.Cohorts1-4 and Cohort 5 (PET sub-study): Any contraindications to the arterial line sampling
20.Cohorts1-5: History or presence of impaired renal function as indicated by clinically significantly abnormal creatinine or BUN and/or urea values, or abnormal urinary constituents (e.g. albuminuria) at the screening visit.
21.Cohorts1-5: Active suicidal ideation
22a.Cohorts1-5: History of drug abuse or harmful alcohol use within the 12 months prior to dosing within the judgement of the investigator, or e

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified