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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04066244




Registration number
NCT04066244
Ethics application status
Date submitted
21/08/2019
Date registered
26/08/2019

Titles & IDs
Public title
Study of Safety and Proof of the Mechanism of BLZ945 in ALS Patients
Scientific title
An Open-label, Adaptive Design Study in Patients With Amyotrophic Lateral Sclerosis (ALS) to Characterize Safety, Tolerability and Brain Microglia Response, as Measured by TSPO Binding, Following Multiple Doses of BLZ945 Using Positron Emission Tomography (PET) With the Radioligand [11C]-PBR28
Secondary ID [1] 0 0
2019-000826-22
Secondary ID [2] 0 0
CBLZ945C12201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Amyotrophic Lateral Sclerosis 0 0
Condition category
Condition code
Neurological 0 0 0 0
Neurodegenerative diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BLZ945

Other: Cohort 1 - BLZ945 300mg

Other: Cohort 2 - BLZ945 600mg

Other: Cohort 3 - BLZ945 1200mg

Other: Cohort 4 - BLZ945 800mg

Other: Cohort 5 Arm #1 - BLZ945 800mg (4 days treatment + 10 days off)

Other: Cohort 5 Arm #2 - BLZ945 800mg (once weekly)


Treatment: Drugs: BLZ945
Investigational drug capsules taken orally or via enteral infusion
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Cohorts 1-4 : Change From Baseline in Volume of Distribution (Vt) in Different Brain Regions for [11C]-PBR28 PET Scan
Timepoint [1] 0 0
Baseline, day 5
Primary outcome [2] 0 0
Cohort 5 (PET Sub-study): Change From Baseline in Volume of Distribution (Vt) in Different Brain Regions for [11C]-PBR28 PET Scan
Timepoint [2] 0 0
Baseline, day 84
Primary outcome [3] 0 0
Cohort 5: Change From Baseline in Esophageal Wall Thickness
Timepoint [3] 0 0
Baseline, Day 84
Primary outcome [4] 0 0
Cohort 5: Cardiac Valve Thickness at Day 84 Compared to Baseline
Timepoint [4] 0 0
Baseline, Day 84
Primary outcome [5] 0 0
Cohort 5: Cardiac Valve Stenosis at Day 84 Compared to Baseline
Timepoint [5] 0 0
Baseline, Day 84
Primary outcome [6] 0 0
Cohort 5: Cardiac Valve Regurgitation Severity at Day 84 Compared to Baseline
Timepoint [6] 0 0
Baseline, Day 84
Primary outcome [7] 0 0
Cohort 5: Change From Baseline in Left Ventricular Ejection Fraction (LVEF)
Timepoint [7] 0 0
Baseline, day 84
Primary outcome [8] 0 0
Cohort 5: Adverse Events Related to Extracellular Matrix (ECM) Accumulation
Timepoint [8] 0 0
Up to Day 84
Secondary outcome [1] 0 0
Cohorts 1-5: Plasma Pharmacokinetics (PK) of BLZ945 - Cmax
Timepoint [1] 0 0
Cohort 1-4: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours after BLZ945 dosing on Day 1 and Day 4. Cohort 5: pre-dose, 1, 2 and 4 hours after BLZ945 dosing on Day 1 (Arm#2 only) and Day 4 (Arm#1 only)
Secondary outcome [2] 0 0
Cohorts 1-5: Plasma Pharmacokinetics (PK) of BLZ945 - Tmax
Timepoint [2] 0 0
Cohort 1-4: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours after BLZ945 dosing on Day 1 and Day 4. Cohort 5: pre-dose, 1, 2 and 4 hours after BLZ945 dosing on Day 1 (Arm#2 only) and Day 4 (Arm#1 only)
Secondary outcome [3] 0 0
Cohorts 1-5: Plasma Pharmacokinetics (PK) of BLZ945 - AUC
Timepoint [3] 0 0
Cohort 1-4: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours after BLZ945 dosing on Day 1 and Day 4. Cohort 5: pre-dose, 1, 2 and 4 hours after BLZ945 dosing on Day 1 (Arm#2 only) and Day 4 (Arm#1 only)
Secondary outcome [4] 0 0
Cohorts 1-4: Plasma Pharmacokinetics (PK) of BLZ945 - T1/2
Timepoint [4] 0 0
Cohort 1-4: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours after BLZ945 dosing on Day 1 and Day 4.
Secondary outcome [5] 0 0
Cohorts 1-4: Renal Clearance (CLR) of BLZ945
Timepoint [5] 0 0
pre-dose, 0-4, 4-8, 8-12 and 12-24 hours after BLZ945 dosing on Day 1 and Day 4
Secondary outcome [6] 0 0
Cohorts 1-5: Number of Patients With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [6] 0 0
From first dose of study treatment up to 32 days after last dose (Day 36) for Cohorts 1-4 and up to 4 weeks after last dose (Day 330) for Cohort 5. *Maximum duration of exposure in Cohort 5 was 302 days. 302 + 28 days of FU=330 days

Eligibility
Key inclusion criteria
* Able to communicate well with the investigator, to understand and comply with the study visits and procedures of the study
* Written informed consent must be obtained before any assessment is performed.
* Male and female participants who are 18 years old or older 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.
* Disease duration from symptoms onset no longer than 48 months at the screening visit.
* Females of childbearing potential must have a negative pregnancy test at screening and/or baseline.
* Treatment with approved ALS therapies is allowed, but participants need to be on a stable dose and regimen for at least 30 days prior to baseline.
* Having completed the Core Treatment Period to be able to continue in the Extended Treatment Period.
Minimum age
18 Years
Maximum age
100 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* A history of clinically significant ECG abnormalities
* Active medical or neurologic diseases other than ALS, that in the opinion of the investigator would limit their participation in the current study.
* 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.
* History of hypersensitivity to any of the study treatments or excipients or to drugs of similar chemical classes.
* Presence of human immunodeficiency virus (HIV) infection based on screening lab results.
* Evidence of active or latent tuberculosis as assessed by Quantiferon testing at the screening visit.
* Positive serology for hepatitis B surface antigen, or hepatitis C antibodies confirmed by an appropriate licensed test at screening.
* 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.
* 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. Participants with cardiac failure class 3 or 4 of the NYHA classification, or history of reduced LVEF or individuals with implanted cardiac pacemaker, or defibrillator.
* Significant hematological laboratory abnormalities.
* Clinical evidence of liver disease or liver injury or any of the following hepatic conditions at the screening visit:
* 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.
* Pregnant or nursing female participants
* 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.
* History or presence of impaired renal function at the screening visit.
* Active suicidal ideation.
* History of drug abuse or harmful alcohol use within the 12 months prior to dosing within the judgement of the investigator, or evidence of such abuse as indicated by the laboratory assays conducted during screening.
* Active GI conditions such as Barrett's esophagus, achalasia, esophageal varices and active or history of esophageal cancer, pre-existing pancreatic disease at screening visit.
* History of active vasculitis or history of autoimmune disease autoimmune disease associated with vasculitis (eg., RA, SLE, Sjögrens disease, scleroderma).
* History or active cardiac valve disorder, congenital valve disease, or other clinical condition that might affect cardiac valve function
* Use of systemic anticoagulation that cannot be temporarily paused before study procedures
* Abnormal values on CT scan or echocardiography, signs of vasculitis, or evidence of a significant medical condition meeting treatment discontinuation criteria will be exclusionary for continuation in the extended treatment period.
* Participants who are planning to initiate treatment with an additional approved ALS therapy in the next 24 weeks are not allowed to continue in the extended treatment period.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/12/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/02/2024
Sample size
Target
Accrual to date
Final
28
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Connecticut
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
Finland
State/province [3] 0 0
Turku
Country [4] 0 0
Sweden
State/province [4] 0 0
Stockholm

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
1-888-669-6682
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT04066244