Safety and Tolerability Study of CTx1000 In Participants With Amyotrophic Lateral Sclerosis

Koanewa: A First in Human, Phase 1b, Open-label, Non-randomised, Single Dose Study to Assess the Safety and Tolerability of CTx1000 in Participants Diagnosed With Amyotrophic Lateral Sclerosis

This clinical study is in participants with Amyotrophic Lateral Sclerosis and is designed to evaluate the safety and tolerability of the gene therapy CTx1000.

CTx1000 is an investigational gene therapy that encodes a degron for targeted degradation of TDP-43 following a single dose intra cisterna magna (ICM) delivery in participants diagnosed with Amyotrophic Lateral Sclerosis (ALS).

Inclusion Criteria:

• Diagnosis of ALS in accordance with the revised El Escorial criteria and TRICALS risk score
• An overall disease duration of ≤ 2 years after the participant's first symptoms
• No or low circulating anti-AAV9 antibodies (titre ≤ 1:50
• Stable dosing with a standard of care ALS medication (eg, riluzole and edaravone) and other prescription medications for 30 days prior to Screening
• Not pregnant or breastfeeding, or willing to cease breastfeeding
• All participants must use a barrier method of contraception

Exclusion Criteria:

• Any participants with genetic forms of ALS, including C9ORF72 repeat carriers, except for TARDBP gene variants, as confirmed by previous clinical history genetic testing
• Any history of myocardial infarction or stroke within 6 months prior to Screening, or uncontrolled diabetes (HbA1C > 9%)
• Positive test for cytomegalovirus, hepatitis C antibody (HCV), hepatitis B surface antigen (HBsAg), human immunodeficiency virus (HIV) antibody.
• Inadequate organ function
• Any participant with a current open tracheostomy