3K3A-APC for Treatment of Amyotrophic Lateral Sclerosis (ALS)

Study Overview
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Brief Summary
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Phase 2 open label trial to investigate the safety and potentially efficacy of 3K3A-APC in patients with Amyotrophic Lateral Sclerosis (ALS).

Detailed Description
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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.

Official Title
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A Phase 2 Open Label Trial of 3K3A-APC in Amyotrophic Lateral Sclerosis

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Drug: 3K3A-APC Protein


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 15mg Dose Group<br>Participants will receive a fixed dose regimen of five doses of 15mg. | Drug: 3K3A-APC Protein<br>* 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.<br>* Other names: 3K3A-APC;|
| Active Comparator: 30mg Dose Group<br>Participants will receive a fixed dose regimen of five doses of 30mg. | Drug: 3K3A-APC Protein<br>* 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.<br>* Other names: 3K3A-APC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 15 Days | 
| 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. | 7 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 7 Days | 
| Monocyte Activation | Change in the level of monocyte activation in the peripheral blood utilising a novel method. | 7 Days | 
| Cytokine Level | Change in cytokine level in serum, plasma and CSF. | 7 Days | 
| Chemokine Level | Change in chemokine level in serum, plasma and CSF. | 7 Days | 
| Neurofilament Level | Change in neurofilament level in serum, plasma and CSF. | 7 Days | 
| Soluble CD14 Level | Change in soluble CD14 level in serum, plasma and CSF. | 7 Days | 
| Kynurenine Level | Change in kynurenine level in serum, plasma and CSF. | 7 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALS, Amyotrophic Lateral Sclerosis, MND, Motor Neurone Disease, 3K3A-APC