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

Amyotrophic Lateral Sclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05039268
• Other study ID #: ZZ-3K3A-202
• Status: Completed
• Phase: Phase 2
• Start date: November 25, 2021
• Est. completion date: September 12, 2022

Study information

• Verified date: September 2022
• Source: Macquarie University, Australia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: September 12, 2022
• Est. primary completion date: September 12, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

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

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• 3K3A-APC Protein
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.

Locations

Country	Name	City	State
Australia	Macquarie University	Macquarie Park	New South Wales

Sponsors (2)

Lead Sponsor	Collaborator
Macquarie University, Australia	ZZ Biotech, LLC

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	Monocyte Activation	Change in the level of monocyte activation in the peripheral blood utilising a novel method.	7 Days
Secondary	Cytokine Level	Change in cytokine level in serum, plasma and CSF.	7 Days
Secondary	Chemokine Level	Change in chemokine level in serum, plasma and CSF.	7 Days
Secondary	Neurofilament Level	Change in neurofilament level in serum, plasma and CSF.	7 Days
Secondary	Soluble CD14 Level	Change in soluble CD14 level in serum, plasma and CSF.	7 Days
Secondary	Kynurenine Level	Change in kynurenine level in serum, plasma and CSF.	7 Days