A Study Evaluating the Safety and Tolerability of QRL-201 in ALS

A Multi-Center, Randomized, Double-Blind Placebo Controlled Multiple-Ascending Dose Study to Evaluate the Safety and Tolerability of QRL-201 in Amyotrophic Lateral Sclerosis, Followed by an Open-Label Extended Dosing Period

The primary objective of this study is to determine the safety and tolerability of multiple doses of QRL-201 in people living with ALS

This first-in-human, Phase 1 study will evaluate the safety, tolerability, and pharmacokinetics (PK) of QRL-201 administered intrathecal (IT) to participants with Amyotrophic Lateral Sclerosis. Two dose escalation cohorts of 8 participants each, followed by an additional 48 participants, receiving the study drug in a 6:2 ratio of QRL-201 to placebo.

Inclusion Criteria (Double-Blind Periods):

• Male or female participants aged 18 to 80 years diagnosed with ALS
• ALS symptom onset within 24 months of Screening
• Slow vital capacity >50%
• Clinical or electrodiagnostic evidence of lower motor neuron involvement
• Not pregnant and not nursing
• Willing and able to practice effective contraception
• Able to tolerate lumbar puncture
• If on approved therapies for the treatment of ALS during the course of the study, must be on a stable dose (at the Sponsor's discretion)

Exclusion Criteria (Double Blind Periods):

• Pathogenic variant, likely pathogenic variant, or variant of uncertain significance in the superoxide dismutase 1 (SOD1) and/or fused in sarcoma (FUS) genes
• Currently enrolled in any other clinical study involving either an investigational product (IP) or off-label use of a drug or device
• Prior exposure to stem cell or gene therapy products
• Any contraindication to intrathecal drug administration
• Abnormal laboratory values deemed clinically significant by the Investigator
• Significant infection or known inflammatory process
• Any sign and/or history of neurological conditions and other neuromuscular disorders that could affect the electrophysiological recordings.
• An EEG that shows signs of abnormal electrical activity (e.g., epilepsy)

Inclusion Criteria (Open-Label Extended Dosing Period):

• Male or female participants in the sporadic ALS and C9orf72 ALS Cohorts of QRL-201-01 who have completed through at least Day 253 of safety follow up in the double-blind study period OR have completed Cohort 1 of Cohort 2
• Not pregnant and not nursing
• Willing and able to practice effective contraception
• Can visit study site for required visits
• Able to tolerate lumbar puncture
• If on approved therapies for the treatment of ALS during the course of the study, must be on a stable dose (at the Sponsor's discretion)

Exclusion Criteria (Open-Label Extended Dosing Period):

• Currently enrolled in any other clinical study involving either an investigational product (IP) or off label use of a drug or device
• Off-label use of drugs or devices that are being used as disease-modifying therapies in ALS
• Participated in another clinical study within 30 days, or 5 half-lives of the previous investigational product, whichever is greater, prior to the first dose
• Prior exposure to stem cell or gene therapy products
• Is not suitable for inclusion in the Open-Label Extended Dosing period of the study, in the opinion of the Investigator
• An EEG that shows signs of abnormal electrical activity (NOTE: Cohort 1 and Cohort 2 participants only)