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

Phase 2

Completed

• Conditions: Amyotrophic Lateral Sclerosis
• Interventions: Drug: 3K3A-APC Protein

• Registration Number: NCT05039268
• Lead Sponsor: Macquarie University, Australia

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.

Study Timeline

• Study First Submitted: 2021-08-23
• Study First Submitted QC: 2021-09-02
• Study First Posted: 2021-09-09
• Study Start: 2021-11-25
• Status Verified: 2022-09
• Primary Completion: 2022-09-12
• Study Completion: 2022-09-12
• Results First Submitted: 2023-09-21
• Results First Submitted QC: 2023-09-21
• Last Update Submitted: 2023-09-21
• Results First Posted: 2023-10-11
• Last Update Posted: 2023-10-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

1. Patients must have clinically definite ALS (Awaji Criteria)
2. Male or female age 18 years and less than 75 years at time of ALS study
3. Symptom onset less than 36 months before screening
4. Diagnosis of ALS less than 24 months before screening
5. Clinically definite Upper Motor Neuron signs

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Exclusion Criteria

1. Current treatment with anticoagulants (e.g., warfarin, novel oral anticoagulants, heparin) that might preclude safe completion of the lumbar puncture
2. Condition that precludes the safe performance of routine lumbar puncture, such as prohibitive lumbar spinal disease, bleeding diathesis, or clinically significant coagulopathy or thrombocytopenia
3. 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)
4. Prolonged prothrombin time or activated partial thromboplastin time >2xULN
5. Severe hypertension or hypotension
6. Glomerular filtration rate (GFR) <35 mL/min
7. Forced vital capacity (FVC) at screening of <50% of predicted
8. Prior exposure to any exogenous form of APC
9. Inability to lie flat for procedures (MRI, PET, LP)
10. Pregnant or lactating during the study period

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
15mg Dose Group	3K3A-APC Protein	Participants will receive a fixed dose regimen of five doses of 15mg.
30mg Dose Group	3K3A-APC Protein	Participants will receive a fixed dose regimen of five doses of 30mg.

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Had Any Serious Adverse Events or Any Adverse Events With Severity Higher Than "Moderate".	15 Days	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	7 Days	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

Name	Time	Method
Monocyte Activation	7 Days	Change in the level of monocyte activation in the peripheral blood utilising a novel method.
Chemokine Level	7 Days	Change in chemokine level in serum, plasma and CSF.
Soluble CD14 Level	7 Days	Change in soluble CD14 level in serum, plasma and CSF.
Diffusion Kurtosis Using MRI Scan	7 Days	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
Cytokine Level	7 Days	Change in cytokine level in serum, plasma and CSF.
Kynurenine Level	7 Days	Change in kynurenine level in serum, plasma and CSF.
Neurofilament Level	7 Days	Change in neurofilament level in serum, plasma and CSF.

Trial Locations

Locations (1)

Macquarie University; 🇦🇺 Macquarie Park, New South Wales, Australia