Amyotrophic Lateral SclerosisPhase 2NCT04066244

Study of Safety and Proof of the Mechanism of BLZ945 in ALS Patients

A Phase 2 study testing BLZ945 in people with Amyotrophic Lateral Sclerosis, run by Novartis Pharmaceuticals at 4 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

It was an open label study to evaluate safety, tolerability and brain microglia response in participants with Amyotrophic Lateral Sclerosis (ALS) following multiple doses of BLZ945. Read more about this study

Who is it for?: Ages 18 to 100 years
Conditions the study is for: Amyotrophic Lateral Sclerosis
What is being tested?: BLZ945
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 28 participants
Where: 4 sitesin 3 countries
Study dates: 30 Dec 2019to 1 Feb 2024
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 100 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Show all 23Show fewer

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.

Trial locations and contacts

4 sites in 3 countries.

Country

City, postcode or hospital

4 sites in 3 countries

United States2 sites

Massachusetts General Hospital
Boston, Massachusetts, 02114
Yale University School of Medicine
New Haven, Connecticut, 06520-8048

Other trials in United States

Finland1 site

Novartis Investigative Site
Turku, 20520

Other trials in Finland

Sweden1 site

Novartis Investigative Site
Stockholm, 14186

Other trials in Sweden

About this study

Official 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

It was an open label study to evaluate safety, tolerability and brain microglia response in participants with Amyotrophic Lateral Sclerosis (ALS) following multiple doses of BLZ945.

Read the detailed description

The purpose of the study was to identify a dose (or doses) of BLZ945, that measurably decrease(s) 18 KDa Translocator Protein (TSPO) binding in the brain of participants with ALS. The study also aimed to evaluate the safety and tolerability of BLZ945 in participants with ALS at different doses and dosing regimens, and safety related effects on extracellular matrix (ECM) accumulation.

This was an exploratory, adaptive , open label study of approximately 16 participants in cohorts of 4 participants per cohort at increasing doses of BLZ945 with the last dose determined after the completion of cohorts 1 to 3.

Each cohort received treatment for 4 days and continued with a 32 day follow up period with an end of study visit at day 36.

After completion of the 4 initial cohorts a fifth cohort was initiated with two parallel arms receiving BLZ945 for up to 12 weeks at two different treatment regimens, either once weekly or 4 days of treatment followed by 10 days off drug.

Conditions: Amyotrophic Lateral Sclerosis
Being tested: BLZ945
Keywords: PET, ALS, Microglia, CSF
Medical subject headings: Amyotrophic Lateral Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BLZ945Drug
Investigational drug capsules taken orally or via enteral infusion

Study groups in NCT04066244
Study group	Role	What they receive
Cohort 1	Other	BLZ945 300mg Receives: Drug: BLZ945
Cohort 2	Other	BLZ945 600mg Receives: Drug: BLZ945
Cohort 3	Other	BLZ945 1200mg Receives: Drug: BLZ945
Cohort 4	Other	BLZ945 800mg Receives: Drug: BLZ945
Cohort 5 Arm #1	Other	BLZ945 800mg (4 days treatment + 10 days off) Receives: Drug: BLZ945
Cohort 5 Arm #2	Other	BLZ945 800mg (once weekly) Receives: Drug: BLZ945

What is being measured

The primary outcome is the main question the study is designed to answer.

Cohorts 1-4 : Change From Baseline in Volume of Distribution (Vt) in Different Brain Regions for [11C]-PBR28 PET Scan
[11C]-PBR28 is a positron emission tomography (PET) radiotracer for the 18 kDa translocator protein (TSPO) that is used to image neuroinflammation in vivo. [11C]PBR28 imaging was used to measure microglial volume at baseline and after BLZ945 treatment in ALS participants.
Relative % change from baseline in volume of distribution (Vt) of [11C]-PBR28 in different brain regions after BLZ945 treatment
Measured: Baseline, day 5
Cohort 5 (PET Sub-study): Change From Baseline in Volume of Distribution (Vt) in Different Brain Regions for [11C]-PBR28 PET Scan
[11C]-PBR28 is a positron emission tomography (PET) radiotracer for the 18 kDa translocator protein (TSPO) that is used to image neuroinflammation in vivo. [11C]PBR28 imaging was used to measure microglial volume at baseline and after BLZ945 treatment in ALS participants.
Relative % change from baseline in volume of distribution (Vt) of [11C]-PBR28 in different brain regions after BLZ945 treatment
Measured: Baseline, day 84
Cohort 5: Change From Baseline in Esophageal Wall Thickness
Mean change from baseline in esophageal wall thickness measured in mm
Measured: Baseline, Day 84
Cohort 5: Cardiac Valve Thickness at Day 84 Compared to Baseline
Cardiac valve thickness on a three point ordinal scale. Categorized by imaging vendor into three semiquantitative (normal, mild-moderate and severe) categories
Measured: Baseline, Day 84
Cohort 5: Cardiac Valve Stenosis at Day 84 Compared to Baseline
Cardiac valve stenosis on a four point ordinal scale. Categorized by imaging vendor into four semiquantitative (normal, mild, moderate and severe) categories
Measured: Baseline, Day 84
Cohort 5: Cardiac Valve Regurgitation Severity at Day 84 Compared to Baseline
Cardiac valve regurgitation severity on a four point ordinal scale. Categorized by imaging vendor into four semiquantitative (normal, mild, moderate and severe) categories
Measured: Baseline, Day 84
Cohort 5: Change From Baseline in Left Ventricular Ejection Fraction (LVEF)
Mean change from baseline in Left Ventricular Ejection Fraction.
LVEF is defined as the percentage of blood volume ejected from the left ventricle during systole (contraction phase) relative to the total volume of blood present in the ventricle at the end of diastole (relaxation phase).
Measured: Baseline, day 84
Cohort 5: Adverse Events Related to Extracellular Matrix (ECM) Accumulation
Number of patients with adverse events related to ECM accumulation
Measured: Up to Day 84

Secondary outcomes (6)

Cohorts 1-5: Plasma Pharmacokinetics (PK) of BLZ945 - Cmax
Measured by Cmax - The maximum plasma concentration of BLZ945
Measured: 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)
Cohorts 1-5: Plasma Pharmacokinetics (PK) of BLZ945 - Tmax
Measured by Tmax - Time to Reach the Maximum Concentration After Drug Administration of BLZ945.
Actual recorded sampling times were taken into consideration for the calculation of PK parameters.
Measured: 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)
Cohorts 1-5: Plasma Pharmacokinetics (PK) of BLZ945 - AUC
Measured by AUC - Area under the curve of BLZ945
AUC0-24h is the AUC calculated from time zero to 24 hours after dosing (end of a dosing interval).
AUClast is the AUC from time zero to the last measurable concentration sampling time.
Measured: 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)
Cohorts 1-4: Plasma Pharmacokinetics (PK) of BLZ945 - T1/2
Measured by T1/2 - The elimination half-life of BLZ945
Measured: 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.
Cohorts 1-4: Renal Clearance (CLR) of BLZ945
Urine renal clearance (CLR) of BLZ945
Measured: pre-dose, 0-4, 4-8, 8-12 and 12-24 hours after BLZ945 dosing on Day 1 and Day 4
Cohorts 1-5: Number of Patients With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Incidence and severity of AEs and SAEs by treatment group.
AE grades to characterize the severity of the AEs were based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5. For CTCAE, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death related to AE
Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Dec 20191 Feb 2024

First posted26 Aug 2019
Study start30 Dec 2019
Primary completion1 Feb 2024
Study completion1 Feb 2024

Why it stopped: Study terminated after assessment of potential benefit-risk from available data

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Model description: This study is an exploratory, adaptive, open-label study of single or multiple cycles of BLZ945 in participants with ALS. Cohorts 1-4 are not randomized, while Cohort 5 is randomized in open label two treatment arms. Cohorts 1-4 have single group design and Cohort 5 has parallel design.
Masking: None (open label)
Enrolment: 28 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04066244
Sponsor's protocol ID: CBLZ945C12201
Other IDs: 2019-000826-22, 2019
Status last verified: Oct 2025
First submitted: 21 Aug 2019
Last updated: 16 Oct 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: 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

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Functional Outcomes and Control Using Synchron BCI - Australia
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Safety, Tolerability, and Pharmacodynamic Exploration of Orelabrutinib in Patients With Amyotrophic Lateral Sclerosis (ALS)
Amyotrophic Lateral Sclerosis (ALS)
Recruiting
Clinical Outcome Assessment for AT & BCI
Spinal Cord Injury, ALS (Amyotrophic Lateral Sclerosis)

All Amyotrophic Lateral Sclerosis trials

Study at a glance

From the registry record, last updated by the sponsor on 16 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official 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
ClinicalTrials.gov ID: NCT04066244
Acronym / sponsor ID: CBLZ945C12201
Conditions: Amyotrophic Lateral Sclerosis
Keywords: PET, ALS, Microglia, CSF
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Study terminated after assessment of potential benefit-risk from available data
Enrolment: 28 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 30 Dec 2019 (actual)
Primary completion: 1 Feb 2024 (actual)
Study completion: 1 Feb 2024 (actual)
First posted: 26 Aug 2019 (actual)
Results: Posted 19 Mar 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

It was an open label study to evaluate safety, tolerability and brain microglia response in participants with Amyotrophic Lateral Sclerosis (ALS) following multiple doses of BLZ945.

Detailed description

Each cohort received treatment for 4 days and continued with a 32 day follow up period with an end of study visit at day 36.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 6
Model description: This study is an exploratory, adaptive, open-label study of single or multiple cycles of BLZ945 in participants with ALS. Cohorts 1-4 are not randomized, while Cohort 5 is randomized in open label two treatment arms. Cohorts 1-4 have single group design and Cohort 5 has parallel design.

Arm	Type	Receives
Cohort 1	Other	Drug: BLZ945BLZ945 300mg
Cohort 2	Other	Drug: BLZ945BLZ945 600mg
Cohort 3	Other	Drug: BLZ945BLZ945 1200mg
Cohort 4	Other	Drug: BLZ945BLZ945 800mg
Cohort 5 Arm #1	Other	Drug: BLZ945BLZ945 800mg (4 days treatment + 10 days off)
Cohort 5 Arm #2	Other	Drug: BLZ945BLZ945 800mg (once weekly)

Who may qualify

Ages: 18 to 100 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

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.

Key exclusion criteria (23 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BLZ945Investigational drug capsules taken orally or via enteral infusion	Drug	Cohort 1, Cohort 2, Cohort 3, Cohort 4, Cohort 5 Arm #1, Cohort 5 Arm #2

Primary outcome

Cohorts 1-4 : Change From Baseline in Volume of Distribution (Vt) in Different Brain Regions for [11C]-PBR28 PET Scan
Time frame: Baseline, day 5
[11C]-PBR28 is a positron emission tomography (PET) radiotracer for the 18 kDa translocator protein (TSPO) that is used to image neuroinflammation in vivo. [11C]PBR28 imaging was used to measure microglial volume at baseline and after BLZ945 treatment in ALS participants. Relative % change from baseline in volume of distribution (Vt) of [11C]-PBR28 in different brain regions after BLZ945 treatment
Cohort 5 (PET Sub-study): Change From Baseline in Volume of Distribution (Vt) in Different Brain Regions for [11C]-PBR28 PET Scan
Time frame: Baseline, day 84
[11C]-PBR28 is a positron emission tomography (PET) radiotracer for the 18 kDa translocator protein (TSPO) that is used to image neuroinflammation in vivo. [11C]PBR28 imaging was used to measure microglial volume at baseline and after BLZ945 treatment in ALS participants. Relative % change from baseline in volume of distribution (Vt) of [11C]-PBR28 in different brain regions after BLZ945 treatment
Cohort 5: Change From Baseline in Esophageal Wall Thickness
Time frame: Baseline, Day 84
Mean change from baseline in esophageal wall thickness measured in mm
Cohort 5: Cardiac Valve Thickness at Day 84 Compared to Baseline
Time frame: Baseline, Day 84
Cardiac valve thickness on a three point ordinal scale. Categorized by imaging vendor into three semiquantitative (normal, mild-moderate and severe) categories
Cohort 5: Cardiac Valve Stenosis at Day 84 Compared to Baseline
Time frame: Baseline, Day 84
Cardiac valve stenosis on a four point ordinal scale. Categorized by imaging vendor into four semiquantitative (normal, mild, moderate and severe) categories
Cohort 5: Cardiac Valve Regurgitation Severity at Day 84 Compared to Baseline
Time frame: Baseline, Day 84
Cardiac valve regurgitation severity on a four point ordinal scale. Categorized by imaging vendor into four semiquantitative (normal, mild, moderate and severe) categories
Cohort 5: Change From Baseline in Left Ventricular Ejection Fraction (LVEF)
Time frame: Baseline, day 84
Mean change from baseline in Left Ventricular Ejection Fraction. LVEF is defined as the percentage of blood volume ejected from the left ventricle during systole (contraction phase) relative to the total volume of blood present in the ventricle at the end of diastole (relaxation phase).
Cohort 5: Adverse Events Related to Extracellular Matrix (ECM) Accumulation
Time frame: Up to Day 84
Number of patients with adverse events related to ECM accumulation

6 secondary outcomes

Cohorts 1-5: Plasma Pharmacokinetics (PK) of BLZ945 - Cmax
Time frame: 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)
Cohorts 1-5: Plasma Pharmacokinetics (PK) of BLZ945 - Tmax
Time frame: 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)
Cohorts 1-5: Plasma Pharmacokinetics (PK) of BLZ945 - AUC
Time frame: 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)
Cohorts 1-4: Plasma Pharmacokinetics (PK) of BLZ945 - T1/2
Time frame: 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.
Cohorts 1-4: Renal Clearance (CLR) of BLZ945
Time frame: pre-dose, 0-4, 4-8, 8-12 and 12-24 hours after BLZ945 dosing on Day 1 and Day 4
Cohorts 1-5: Number of Patients With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: 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

Results and safety

Results posted to the registry on 19 Mar 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
BLZ945 300mg - Cohort 1 (Part 1)	4	4
BLZ945 600mg - Cohort 2 (Part 1)	4	4
BLZ945 800mg - Cohort 4 (Part 1)	4	4
BLZ945 1200mg - Cohort 3 (Part 1)	4	4
BLZ945 800mg - Cohort 5 Arm #1 (Part 2)	0	0
BLZ945 800mg - Cohort 5 Arm #2 (Part 2)	0	0

Primary outcome: Cohorts 1-4 : Change From Baseline in Volume of Distribution (Vt) in Different Brain Regions for [11C]-PBR28 PET Scan

Time frame: Baseline, day 5. Mean (Standard Deviation). Unit: Percent change from baseline

Measure	BLZ945 300mg - Cohort 1 (Part 1) n = 3	BLZ945 600mg - Cohort 2 (Part 1) n = 3	BLZ945 800mg - Cohort 4 (Part 1) n = 4	BLZ945 1200mg - Cohort 3 (Part 1) n = 2
Precentral gyrus - day 5	0.67 (33.825)	-20.33 (16.458)	9.90 (31.570)	-9.63 (1.516)
Basal Ganglia - day 5	-3.70 (22.729)	-15.18 (16.343)	13.27 (35.504)	-10.73 (5.872)
Brain Stem - day 5	-7.10 (20.890)	-10.00 (13.464)	50.56 (100.838)	-16.69 (61.674)
Cerebellar White Matter - day 5	-4.41 (20.678)	-14.11 (11.904)	27.65 (60.112)	-16.87 (4.874)
Cerebellum - day 5	-3.53 (20.459)	-10.06 (8.365)	17.52 (44.628)	-11.78 (3.854)
Frontal Lobe - day 5	1.33 (30.101)	-18.67 (15.881)	9.10 (29.745)	-9.70 (0.224)
Occipital Lobe - day 5	-3.01 (23.217)	-11.50 (10.457)	14.18 (36.595)	-5.87 (0.292)
Thalamus - day 5	-8.00 (22.581)	-14.85 (13.466)	13.89 (42.938)	-14.14 (3.521)

Population analysed: PD analysis set, all participants in cohorts 1-4 with available PD data and no protocol deviations with relevant impact on PD data and with a valid assessment of the outcome measure.

Primary outcome: Cohort 5 (PET Sub-study): Change From Baseline in Volume of Distribution (Vt) in Different Brain Regions for [11C]-PBR28 PET Scan

Time frame: Baseline, day 84. Mean (Standard Deviation). Unit: Percent change from baseline

Measure	BLZ945 800mg - Cohort 5 Arm #1 (Part 2) n = 1	BLZ945 800mg - Cohort 5 Arm #2 (Part 2) n = 0
Precentral gyrus - day 84	-21.95	–
Basal Ganglia - day 84	-17.80	–
Brain Stem - day 84	-26.10	–
Cerebellar White Matter - day 84	-22.40	–
Cerebellum - day 84	-19.40	–
Frontal Lobe - day 84	-21.53	–
Occipital Lobe - day 84	-17.76	–
Thalamus - day 84	-29.39	–

Population analysed: PD analysis set, all participants in cohort 5 with available PD data and no protocol deviations with relevant impact on PD data and with a valid assessment of the outcome measure.

Primary outcome: Cohort 5: Change From Baseline in Esophageal Wall Thickness

Time frame: Baseline, Day 84. Mean (Standard Deviation). Unit: mm

Measure	BLZ945 800mg - Cohort 5 Arm #1 (Part 2) n = 4	BLZ945 800mg - Cohort 5 Arm #2 (Part 2) n = 2
Wall thickness average	0.258 (0.7990)	0.758 (2.1708)
Lower third Wall Thickness	0.040 (0.9475)	-1.400 (2.9981)
Middle third Wall Thickness	0.235 (0.0212)	2.795 (2.6234)
Upper third Wall Thickness	0.500 (1.4284)	0.880 (0.8910)

Population analysed: Full analysis set, participants in cohort 5 that received any study drug with a valid assessment for the outcome measure

Primary outcome: Cohort 5: Cardiac Valve Thickness at Day 84 Compared to Baseline

Time frame: Baseline, Day 84. Count of participants. Unit: Participants

Measure	BLZ945 800mg - Cohort 5 Arm #1 (Part 2) n = 6	BLZ945 800mg - Cohort 5 Arm #2 (Part 2) n = 6
Aortic valve thickness - Baseline: Normal	6	6
Aortic valve thickness - Baseline: Mild- Moderate	0	0
Aortic valve thickness - Day 84: Normal	2	2
Aortic valve thickness - Day 84: Mild- Moderate	0	0
Mitral valve thickness - Baseline: Normal	6	5
Mitral valve thickness - Baseline: Mild- Moderate	0	1
Mitral valve thickness - Day 84: Normal	2	2
Mitral valve thickness - Day 84: Mild- Moderate	0	0

Population analysed: Full analysis set, participants in cohort 5 that received any study drug with a valid assessment for the outcome measure

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: 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. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
BLZ945 300mg	0 of 4 (0%)	2 of 4 (50%)	0 of 4
BLZ945 600mg	0 of 4 (0%)	2 of 4 (50%)	0 of 4
BLZ945 800mg	0 of 4 (0%)	4 of 4 (100%)	0 of 4
BLZ945 1200mg	1 of 4 (25%)	4 of 4 (100%)	0 of 4
Arm 1 (4/10)	0 of 6 (0%)	6 of 6 (100%)	0 of 6
Arm 2 (4/10) QW	4 of 6 (66.7%)	6 of 6 (100%)	2 of 6
Total	5 of 28 (17.9%)	24 of 28 (85.7%)	2 of 28

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
A Plain Language Trial Summary is available on www.novctrd.comLink provided by the sponsor.
Individual participant dataSharing planned: Yes. 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

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

4 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing BLZ945 in people with Amyotrophic Lateral Sclerosis, run by Novartis Pharmaceuticals at 4 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 16 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States, Finland, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cohorts 1-4 : Change From Baseline in Volume of Distribution (Vt) in Different Brain Regions for [11C]-PBR28 PET Scan (time frame: Baseline, day 5). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04066244.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2025.