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

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.

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

Day-of-consent through end-of-participation, 15 days

Adverse events are continuously collected from day-of-consent through end-of-participation for each participant.

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).