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

NCT05039268 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: ZZ-3K3A-202
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Amyotrophic Lateral Sclerosis

Keywords

ALS; Amyotrophic Lateral Sclerosis; MND; Motor Neurone Disease; 3K3A-APC

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (7)

• Diffusion Kurtosis Using MRI Scan

  7 Days

• Monocyte Activation

  7 Days

• Cytokine Level

  7 Days

• Chemokine Level

  7 Days

• Neurofilament Level

  7 Days

Study Arms (2)

15mg Dose Group

ACTIVE COMPARATOR

Participants will receive a fixed dose regimen of five doses of 15mg.

Drug: 3K3A-APC Protein

30mg Dose Group

ACTIVE COMPARATOR

Participants will receive a fixed dose regimen of five doses of 30mg.

Drug: 3K3A-APC Protein

Interventions

3K3A-APC Protein DRUG

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.

Also known as: 3K3A-APC

15mg Dose Group; 30mg Dose Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Macquarie University, Australia: lead
• ZZ Biotech, LLC: collaborator

Study Sites (1)

Macquarie University

Macquarie Park, New South Wales, 2113, Australia

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

3K3A-APC protein

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Limitations and Caveats

The main limitation of the study is the small number of participants in the \[18F\]FEMPA PET analysis, which is one of the primary outcomes. In total, only 8 participants (5 in the 15mg group and 3 in the 30mg group) were analysed. The reasons for not including in the analysis are: PET scan data loss due to technical issues (1 participant), PET scan not being performed due to FEMPA production/QC failure (1 participant), and data being uninterpretable at analysis stage (6 participants).

Results Point of Contact

• Title: Richard Gan
• Organization: Macquarie University

richard.gan@mq.edu.au

+61 2 9812 3739

Study Officials

• Dominic Rowe, PhD, MD

  Macquarie University, Australia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2021
• First Posted: September 9, 2021
• Study Start: November 25, 2021
• Primary Completion: September 12, 2022
• Study Completion: September 12, 2022
• Last Updated: October 11, 2023
• Results First Posted: October 11, 2023

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)