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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 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 - Dose 1 of BLZ945

Other: Cohort 2 - Dose 2 of BLZ945

Other: Cohort 3 - Dose 3 of BLZ945

Other: Cohort 4 - Dose 4 of BLZ945

Other: Cohort 5 Arm #1 - Dose 4, Regimen 1 of BLZ945

Other: Cohort 5 Arm #2 - Dose 4, Regimen 2 of BLZ945

Other: Cohort 5 Arm #1 extended treatment period - Dose 4, Regimen 1 of BLZ945

Other: Cohort 5 Arm #2 extended treatment period - Dose 4, Regimen 2 of BLZ945


Treatment: Drugs: BLZ945
Investigational drug
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Cohorts 1-4 and Cohort 5 (PET sub-study): Change from baseline in volume of distribution (Vt) in different brain regions for [11C]-PBR28 PET scan
Timepoint [1] 0 0
Baseline, up to Day 85
Primary outcome [2] 0 0
Cohort 5: Change from baseline in esophageal wall thickness
Timepoint [2] 0 0
Up to Day 85
Primary outcome [3] 0 0
Cohort 5: Change from baseline in cardiac valve thickness
Timepoint [3] 0 0
Up to Day 85
Primary outcome [4] 0 0
Cohort 5: Change from baseline in cardiac valve function
Timepoint [4] 0 0
Up to Day 85
Primary outcome [5] 0 0
Cohort 5: Change from baseline in Left Ventricular Ejection Fraction
Timepoint [5] 0 0
Up to Day 85
Primary outcome [6] 0 0
Cohort 5: Adverse events related to ECM accumulation
Timepoint [6] 0 0
Up to Day 85
Secondary outcome [1] 0 0
Cohorts 1-5: Plasma Pharmacokinetics (PK) of BLZ945 - Cmax
Timepoint [1] 0 0
Day 1; up to Day 74
Secondary outcome [2] 0 0
Cohorts 1-5: Plasma Pharmacokinetics (PK) of BLZ945 - Tmax
Timepoint [2] 0 0
Day 1; up to Day 74
Secondary outcome [3] 0 0
Cohorts 1-5: Plasma Pharmacokinetics (PK) of BLZ945 - AUC
Timepoint [3] 0 0
Day 1; up to Day 74
Secondary outcome [4] 0 0
Cohorts 1-5: Plasma Pharmacokinetics (PK) of BLZ945 - T1/2
Timepoint [4] 0 0
Day 1; up to Day 74
Secondary outcome [5] 0 0
Cohorts 1-4: Renal Clearance (CLR) of BLZ945
Timepoint [5] 0 0
Day 1; up to Day 7
Secondary outcome [6] 0 0
Cohorts 1-5: CYP2C8 genotyping
Timepoint [6] 0 0
Day 1
Secondary outcome [7] 0 0
Cohorts 1-5: Number of patients with adverse events
Timepoint [7] 0 0
Up to Day 281

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
No limit
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
Single group
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)
QLD,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Herston
Recruitment hospital [2] 0 0
Novartis Investigative Site - Cauldfield
Recruitment hospital [3] 0 0
Novartis Investigative Site - Heidelberg
Recruitment postcode(s) [1] 0 0
4029 - Herston
Recruitment postcode(s) [2] 0 0
3162 - Cauldfield
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
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
novartis.email@novartis.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment
Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04066244