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

Phase 1

Recruiting

• Conditions: Amyotrophic Lateral Sclerosis
• Interventions: Drug: Multiple ascending doses of QRL-201; Drug: Placebo; Drug: Multiple ascending doses of Placebo; Drug: QRL-201

• Registration Number: NCT05633459
• Lead Sponsor: QurAlis Corporation

Brief Summary

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

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 Timeline

• Study First Submitted: 2022-11-21
• Study First Submitted QC: 2022-11-21
• Study First Posted: 2022-12-01
• Study Start: 2022-12-16
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-07
• Last Update Posted: 2025-04-08
• Primary Completion: 2026-08-31
• Study Completion: 2026-08-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 64

Inclusion Criteria

• 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

• 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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
QRL-201: Sporadic ALS	Multiple ascending doses of QRL-201	Multiple-ascending doses of QRL-201 will be intrathecally administered to individuals with ALS.
Placebo: C9orf72-ALS	Placebo	Placebo comparator will be intrathecally administered to individuals with C9orf72-ALS.
Placebo: Sporadic ALS	Multiple ascending doses of Placebo	Multiple-ascending doses of placebo comparator will be intrathecally administered to individuals with ALS.
QRL-201: C9orf72-ALS	QRL-201	QRL-201 will be intrathecally administered to individuals with C9orf72-ALS.

Primary Outcome Measures

Name	Time	Method
Number of participants with one or more treatment emergent adverse events and serious adverse events	Baseline through Day 421 [End of Study Visit	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.

Secondary Outcome Measures

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

Trial Locations

Locations (14)

Universitaire Ziekenhuizen Leuven (UZ Leuven); 🇧🇪 Leuven, Belgium

University of Calgary; 🇨🇦 Calgary, Alberta, Canada

University of Alberta; 🇨🇦 Edmonton, Alberta, Canada

Sunnybrook Health Science Centre; 🇨🇦 Toronto, Ontario, Canada

CHUM - Hopital Notre-Dame; 🇨🇦 Montréal, Quebec, Canada

Montreal Neurological Institute-Hospital; 🇨🇦 Montréal, Quebec, Canada

Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE); 🇩🇪 Bonn, North Rhine-Westphalia, Germany

Charité Research Organisation; 🇩🇪 Berlin, Germany

University Hospital Schleswig-Holstein (UKSH) Campus Lübeck, Department for Neurology/ Precision Neurology; 🇩🇪 Lübeck, Germany

Universitätsklinikum Ulm; 🇩🇪 Ulm, Germany

St James's Hospital; 🇮🇪 Dublin, Ireland

Universitair Medisch Centrum Utrecht; 🇳🇱 Utrecht, Netherlands

Kings College Hospital NHS Foundation Trust; 🇬🇧 London, United Kingdom

The University of Sheffield, Royal Hallamshire Hospital; 🇬🇧 Sheffield, United Kingdom