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

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

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

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: 3K3A-APC Protein

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 Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Macquarie Park, New South Wales, Australia, 2113
      • Macquarie University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 15mg Dose Group; Participants will receive a fixed dose regimen of five doses of 15mg.	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.; Other Names: 3K3A-APC
Active Comparator: 30mg Dose Group; Participants will receive a fixed dose regimen of five doses of 30mg.	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.; Other Names: 3K3A-APC

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Macquarie University, Australia
• Collaborators: ZZ Biotech, LLC
• Investigators: Principal Investigator: Dominic Rowe, PhD, MD, Macquarie University, Australia

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2021
• Primary Completion (Actual): September 12, 2022
• Study Completion (Actual): September 12, 2022

Study Registration Dates

• First Submitted: August 23, 2021
• First Submitted That Met QC Criteria: September 2, 2021
• First Posted (Actual): September 9, 2021

Study Record Updates

• Last Update Posted (Actual): October 11, 2023
• Last Update Submitted That Met QC Criteria: September 21, 2023
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Amyotrophic Lateral Sclerosis; ALS; Motor Neurone Disease; MND; 3K3A-APC
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: ZZ-3K3A-202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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