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

Study Overview

• Status: Active, not recruiting
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: Placebo; Drug: Multiple ascending doses of QRL-201; Drug: Multiple ascending doses of Placebo; Drug: QRL-201; Drug: QRL-201

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, B-3000
    • Universitaire Ziekenhuizen Leuven (UZ Leuven)
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 1N4
      • University Of Calgary
    • Edmonton, Alberta, Canada, T6G 2G3
      • University of Alberta
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Science Centre
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
      • CHUM - Hopital Notre-Dame
    • Montreal, Quebec, Canada, H3A 2B4
      • Montreal Neurological Institute-Hospital
• Germany
  • Berlin, Germany, 10117
    • Charité Research Organisation
  • Lübeck, Germany
    • University Hospital Schleswig-Holstein (UKSH) Campus Lübeck, Department for Neurology/ Precision Neurology
  • Ulm, Germany, 89081
    • Universitatsklinikum Ulm
  • North Rhine-Westphalia
    • Bonn, North Rhine-Westphalia, Germany, 53127
      • Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE)
• Ireland
  • Dublin, Ireland, D08 A978
    • St James's Hospital
• Netherlands
  • Utrecht, Netherlands
    • Universitair Medisch Centrum Utrecht
• United Kingdom
  • London, United Kingdom, WC1N 3BG
    • National Hospital For Neurology and Neurosurgery
  • London, United Kingdom, SE5 9RS
    • Kings College Hospital NHS Foundation Trust
  • United Kingdom
    • Sheffield, United Kingdom, United Kingdom, S10 2JF
      • The University of Sheffield, Royal Hallamshire Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: QRL-201: Sporadic ALS; Multiple-ascending doses of QRL-201 will be intrathecally administered to individuals with ALS.	Drug: Multiple ascending doses of QRL-201; Multiple ascending doses of QRL-201 will be intrathecally administered to individuals with sporadic ALS.
Placebo Comparator: Placebo: Sporadic ALS; Multiple-ascending doses of placebo comparator will be intrathecally administered to individuals with ALS.	Drug: Multiple ascending doses of Placebo; Multiple ascending doses of placebo comparator will be intrathecally administered to individuals with sporadic ALS.
Experimental: QRL-201: C9orf72-ALS; QRL-201 will be intrathecally administered to individuals with C9orf72-ALS.	Drug: QRL-201; QRL-201 will be intrathecally administered to individuals with C9orf72 ALS.; Drug: QRL-201; QRL-201 will be intrathecally administered to all participants who enter the Open-Label Extended Dosing Period.
Placebo Comparator: Placebo: C9orf72-ALS; Placebo comparator will be intrathecally administered to individuals with C9orf72-ALS.	Drug: Placebo; Placebo comparator will be intrathecally administered to individuals with C9orf72 ALS.
Experimental: QRL-201: Open-label Extended Dosing Period; Open-label QRL-201 will be intrathecally administered to individuals with ALS who qualify for and enter the open-label extended dosing period.	Drug: QRL-201; QRL-201 will be intrathecally administered to individuals with C9orf72 ALS.; Drug: QRL-201; QRL-201 will be intrathecally administered to all participants who enter the Open-Label Extended Dosing Period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with one or more treatment emergent adverse events and serious adverse events	Endpoints: A summary of treatment emergent adverse events, serious adverse events, and other non-serious adverse events, regardless of causality, will be reported in the Reported Adverse Events module.	Baseline through Day 421 [End of Study Visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (plasma): Time of maximum concentration (Tmax) of QRL-201	Endpoints: PK: Tmax of QRL-201	Predose up to 24 hours postdose
Pharmacokinetics (plasma): Maximum observed concentration of QRL-201 (Cmax)	Endpoints: PK: Cmax of QRL-201	Predose up to 24 hours post dose
Pharmacokinetics (plasma): Area under the concentration time curve from zero to infinity (AUCinf) of QRL-201	Endpoints: PK: AUC (0-inf) of QRL-201	Predose up to 24 hours post dose

Collaborators and Investigators

• Sponsor: QurAlis Corporation
• Investigators: Study Director: Manoj Malhotra, MD, QurAlis Corporation

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2022
• Primary Completion (Estimated): May 29, 2026
• Study Completion (Estimated): November 30, 2027

Study Registration Dates

• First Submitted: November 21, 2022
• First Submitted That Met QC Criteria: November 21, 2022
• First Posted (Actual): December 1, 2022

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: ALS, Stathmin-2, STMN2, ASO, Antisense Oligonucleotide
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Nutritional and Metabolic Diseases; Amyotrophic Lateral Sclerosis; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: QRL-201-01

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.: No