Back to results3K3A-APC for Treatment of Amyotrophic Lateral Sclerosis (ALS)
Primary Purpose
Amyotrophic Lateral Sclerosis
Status
Completed
Phase
Phase 2
Locations
Australia
Study Type
Interventional
Intervention
3K3A-APC Protein
Sponsored by
About this trial
This is an interventional treatment trial for Amyotrophic Lateral Sclerosis focused on measuring ALS, Amyotrophic Lateral Sclerosis, MND, Motor Neurone Disease, 3K3A-APC
Eligibility Criteria
Inclusion Criteria:
- Patients must have clinically definite ALS (Awaji Criteria)
- Male or female age 18 years and less than 75 years at time of ALS study
- Symptom onset less than 36 months before screening
- Diagnosis of ALS less than 24 months before screening
- Clinically definite Upper Motor Neuron signs
Exclusion Criteria:
- Current treatment with anticoagulants (e.g., warfarin, novel oral anticoagulants, heparin) that might preclude safe completion of the lumbar puncture
- Condition that precludes the safe performance of routine lumbar puncture, such as prohibitive lumbar spinal disease, bleeding diathesis, or clinically significant coagulopathy or thrombocytopenia
- Use of investigational drugs or devices within 60 days prior to Baseline (dietary supplements taken outside of a clinical trial are not exclusionary, e.g., coenzyme Q10)
- Prolonged prothrombin time or activated partial thromboplastin time >2xULN
- Severe hypertension or hypotension
- Glomerular filtration rate (GFR) <35 mL/min
- Forced vital capacity (FVC) at screening of <50% of predicted
- Prior exposure to any exogenous form of APC
- Inability to lie flat for procedures (MRI, PET, LP)
- Pregnant or lactating during the study period
Sites / Locations
- Macquarie University
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
15mg Dose Group
30mg Dose Group
Arm Description
Participants will receive a fixed dose regimen of five doses of 15mg.
Participants will receive a fixed dose regimen of five doses of 30mg.
Outcomes
Primary Outcome Measures
Number of Participants Who Had Any Serious Adverse Events or Any Adverse Events With Severity Higher Than "Moderate".
Number of participants who had any serious adverse events or any adverse events with severity higher than "moderate", as determined by the Principal Investigator, using the composite safety assessment including clinical laboratory testing (full blood count, biochemistry, coagulation, iron study, CSF analysis and ECG), physical examination and self-reporting of adverse events. All clinical significant findings in the composite safety assessment were reported as adverse events.
Percentage of Change in PERSI Score in the Motor Cortex Before and After Dosing
PERSI (Parametric Estimation of Reference Signal Intensity) score is the measurement of microglial activation in the motor cortex utilising serial [18F]FEMPA PET imaging. The percentage of change in PERSI score before and after dosing in the two (2) dose cohorts is calculated.
Secondary Outcome Measures
Diffusion Kurtosis Using MRI Scan
Change in diffusion kurtosis using MRI scan of the brain to determine whether the blood brain barrier integrity can be measured in ALS by Magnetic Resonance Imaging, and whether 3K3A-APC is able to repair it
Monocyte Activation
Change in the level of monocyte activation in the peripheral blood utilising a novel method.
Cytokine Level
Change in cytokine level in serum, plasma and CSF.
Chemokine Level
Change in chemokine level in serum, plasma and CSF.
Neurofilament Level
Change in neurofilament level in serum, plasma and CSF.
Soluble CD14 Level
Change in soluble CD14 level in serum, plasma and CSF.
Kynurenine Level
Change in kynurenine level in serum, plasma and CSF.
Full Information
NCT ID
NCT05039268
First Posted
August 23, 2021
Last Updated
September 21, 2023
Sponsor
Macquarie University, Australia
Collaborators
ZZ Biotech, LLC
1. Study Identification
Unique Protocol Identification Number
NCT05039268
Brief Title
3K3A-APC for Treatment of Amyotrophic Lateral Sclerosis (ALS)
Official Title
A Phase 2 Open Label Trial of 3K3A-APC in Amyotrophic Lateral Sclerosis
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Completed
Study Start Date
November 25, 2021 (Actual)
Primary Completion Date
September 12, 2022 (Actual)
Study Completion Date
September 12, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Macquarie University, Australia
Collaborators
ZZ Biotech, LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Phase 2 open label trial to investigate the safety and potentially efficacy of 3K3A-APC in patients with Amyotrophic Lateral Sclerosis (ALS).
Detailed Description
This Phase 2 open label trial seeks to investigate whether a novel therapy named 3K3A-APC is safe and potentially effective in patients with Amyotrophic Lateral Sclerosis (ALS). A total of 16 patients with ALS will be enrolled into 2 dose cohorts with five doses of 15mg or 30mg doses given 12 hours apart in each cohort. The primary study outcomes are to ensure the safety and tolerability of 3K3AAPC in ALS patients, and to determine whether 3K3A-APC is able to reduce the pathological changes that might possibly cause ALS.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyotrophic Lateral Sclerosis
Keywords
ALS, Amyotrophic Lateral Sclerosis, MND, Motor Neurone Disease, 3K3A-APC
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
15mg Dose Group
Arm Type
Active Comparator
Arm Description
Participants will receive a fixed dose regimen of five doses of 15mg.
Arm Title
30mg Dose Group
Arm Type
Active Comparator
Arm Description
Participants will receive a fixed dose regimen of five doses of 30mg.
Intervention Type
Drug
Intervention Name(s)
3K3A-APC Protein
Other Intervention Name(s)
3K3A-APC
Intervention Description
3K3A-APC with intravenous dosing of five doses of either 15mg or 30mg at 12 hourly interval. The first 8 patients will receive 15mg dose, and the next 8 patients will receive 30mg dose.
Primary Outcome Measure Information:
Title
Number of Participants Who Had Any Serious Adverse Events or Any Adverse Events With Severity Higher Than "Moderate".
Description
Number of participants who had any serious adverse events or any adverse events with severity higher than "moderate", as determined by the Principal Investigator, using the composite safety assessment including clinical laboratory testing (full blood count, biochemistry, coagulation, iron study, CSF analysis and ECG), physical examination and self-reporting of adverse events. All clinical significant findings in the composite safety assessment were reported as adverse events.
Time Frame
15 Days
Title
Percentage of Change in PERSI Score in the Motor Cortex Before and After Dosing
Description
PERSI (Parametric Estimation of Reference Signal Intensity) score is the measurement of microglial activation in the motor cortex utilising serial [18F]FEMPA PET imaging. The percentage of change in PERSI score before and after dosing in the two (2) dose cohorts is calculated.
Time Frame
7 Days
Secondary Outcome Measure Information:
Title
Diffusion Kurtosis Using MRI Scan
Description
Change in diffusion kurtosis using MRI scan of the brain to determine whether the blood brain barrier integrity can be measured in ALS by Magnetic Resonance Imaging, and whether 3K3A-APC is able to repair it
Time Frame
7 Days
Title
Monocyte Activation
Description
Change in the level of monocyte activation in the peripheral blood utilising a novel method.
Time Frame
7 Days
Title
Cytokine Level
Description
Change in cytokine level in serum, plasma and CSF.
Time Frame
7 Days
Title
Chemokine Level
Description
Change in chemokine level in serum, plasma and CSF.
Time Frame
7 Days
Title
Neurofilament Level
Description
Change in neurofilament level in serum, plasma and CSF.
Time Frame
7 Days
Title
Soluble CD14 Level
Description
Change in soluble CD14 level in serum, plasma and CSF.
Time Frame
7 Days
Title
Kynurenine Level
Description
Change in kynurenine level in serum, plasma and CSF.
Time Frame
7 Days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients must have clinically definite ALS (Awaji Criteria)
Male or female age 18 years and less than 75 years at time of ALS study
Symptom onset less than 36 months before screening
Diagnosis of ALS less than 24 months before screening
Clinically definite Upper Motor Neuron signs
Exclusion Criteria:
Current treatment with anticoagulants (e.g., warfarin, novel oral anticoagulants, heparin) that might preclude safe completion of the lumbar puncture
Condition that precludes the safe performance of routine lumbar puncture, such as prohibitive lumbar spinal disease, bleeding diathesis, or clinically significant coagulopathy or thrombocytopenia
Use of investigational drugs or devices within 60 days prior to Baseline (dietary supplements taken outside of a clinical trial are not exclusionary, e.g., coenzyme Q10)
Prolonged prothrombin time or activated partial thromboplastin time >2xULN
Severe hypertension or hypotension
Glomerular filtration rate (GFR) <35 mL/min
Forced vital capacity (FVC) at screening of <50% of predicted
Prior exposure to any exogenous form of APC
Inability to lie flat for procedures (MRI, PET, LP)
Pregnant or lactating during the study period
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dominic Rowe, PhD, MD
Organizational Affiliation
Macquarie University, Australia
Official's Role
Principal Investigator
Facility Information:
Facility Name
Macquarie University
City
Macquarie Park
State/Province
New South Wales
ZIP/Postal Code
2113
Country
Australia
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
3K3A-APC for Treatment of Amyotrophic Lateral Sclerosis (ALS)
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